bluuebunny/crossref_metadata_2025 huggingface dataset:
Karyotypic characterization of colorectal adenocarcinomas
Authors: Bardi Georgia , Sukhikh Tatiana , Pandis Nikos , Fenger Claus , Kronborg Ole , Heim Sverre
Published: February 2007

Cytogenetic analysis of short‐term cultures from 52 primary colorectal adenocarcinomas revealed clonal chromosome aberrations in 45 tumors, whereas the remaining 7 had a normal karyotype. More than 1 abnormal clone was detected in 26 tumors; in 18 of them, the clones were cytogenetically unrelated. The modal chromosome number was near‐diploid in 32 tumors and near‐triploid to near‐tetraploid in 13. Only numerical aberrations were identified in 13 carcinomas, only structural aberrations in 3, and 29 had both numerical and structural changes. The most common numerical abnormalities were, in order of decreasing frequency, gains of chromosomes 7, 13, 20, and Y and losses of chromosomes 18, Y, 14, and 15. The structural changes most often affected chromosomes 1, 17, 8, 7, and 13. The most frequently rearranged chromosome bands were, in order of decreasing frequency, 13q10, 17p10, 1p22, 8q10, 17p11, 7q11, 1p33, 7p22, 7q32, 12q24, 16p13, and 19p13. Frequently recurring aberrations affecting these bands were del(1)(p22), i(8)(q10), i(13)(q10), and add(17)(p11–13). The most common partial gains were from chromosome arms 8q, 13q, and 17q and the most common partial losses from chromosome arms 1p, 8p, 13p, and 17p. A correlation analysis between the karyotype and the clinicopathologic features in our total material, which consists of altogether 153 colorectal carcinomas, including 116 with an abnormal karyotype, showed a statistically significant association (P < 0.05) between the karyotype and tumor grade and site. Carcinomas with structural chromosome rearrangements were often poorly differentiated; well and moderately differentiated tumors often had only numerical aberrations or normal karyotypes. Abnormal karyotypes were more common in rectal carcinomas than in carcinomas situated higher up. Near‐triploid to near‐tetraploid karyotypes were more than twice as frequent in tumors of the distal colon as in those of the proximal colon and rectum. The cytogenetic data indicate that carcinomas located in the proximal colon and rectum, which often are near‐diploid with simple numerical changes and cytogenetically unrelated clones, probably arise through different mechanisms than do tumors located in the distal colon, which more often have complex near‐triploid to near‐tetraploid karyotypes.
11q13 Amplification in local recurrence of human primary breast cancer
Authors: Champème Marie‐Hélène , Bièche Ivan , Lizard Sarab , Lidereau Rosette
Published: February 2007

Breast cancer can relapse both locally and at distant metastatic sites. The mechanism of Iocal recurrence is unknown, but seems to be due not only to the number of residual cancer cells (inadequate irradiation or surgery), but also to their genetically determined malignant potential. To identify genetic alterations associated with local recurrence risk in breast carcinoma, we analyzed 28 local recurrences and 173 primary breast tumors for the ten most frequently altered genetic regions in breast carcinomas, i.e., loss of heterozygosity on chromosomal arms 1p, 3p, 7q, 11p, 17p, 17q, and 18q, and amplification of the MYC and ERBB2 protooncogenes and of genes in 11q13. Only INT2/FGF3 and CCND1, located in 11q13, were more frequently amplified in local recurrences than in primary tumors (39% vs. 17%; P < 0.01). Moreover, recurrence‐free survival was shorter when the 11q13 region was amplified. These results suggest that one or more genes located in 11q13 play an important role in local relapses of breast cancer.
Atypical cytogenetic aberrations in two childhood peripheral primitive neuroectodermal Tumors
Authors: Murray Jeffrey C. , Langston Claire , Dreyer Zoann E. , Stephenson Charles T. , Pokorny William J. , Horowitz Marc E. , Cooley Linda D.
Published: February 2007

Atypical cytogenetic abnormalities were detected in peripheral primitive neuroectodermal tumors (PPNET) of the extremity in two children. One had an osseous tumor with a balanced reciprocal translocation, t(5;9)(q22;q32), and had a complete response to therapy. The other had a non‐osseous tumor with an interstitial deletion, del(18)(q12.2q21.2), was resistant to combination therapy, and at autopsy had evidence of possible clonal evolution with the karyotype 46,XX der(8)t (8;8)(p11.2;q13), inv(16)(p13.2q12), del(18)(q12.2q21.2). Neither tumor demonstrated the t(11;22)(q24;q12) typically found in Ewing's sarcoma and PPNET, suggesting heterogeneity of the cytogenetic aberrations seen in this rare childhood malignancy.
Consistent presence of isochromosome 7q in hepatosplenic t γ/δ lymphoma: A new cytogenetic‐clinicopathologic entity
Authors: Wang Chuan‐Cheng , Tien Hwei‐Fang , Lin Ming‐Tseh , Su Ih‐Jen , Wang Chiu‐Hwa , Chuang Sou‐Ming , Shen Ming‐Ching , Liu Chen‐Hui
Published: February 2007

Peripheral T‐cell lymphoma (PTL), which is characterized by hepatosplenic presentation and the γ/δ T‐cell receptor (TCR) phenotype on the malignant cells, is a rare but distinct subtype of non‐Hodgkin's lymphomas. Little is known about the chromosomal changes in these lymphomas. We report the cytogenetic analysis of three patients who had neoplastic proliferation of T γ/δ cells in the spleen, bone marrow, and liver, but not in lymph nodes or skin. Isochromosome 7q and trisomy 8 were observed in all three patients. Isochromosome 7q as the sole abnormality has been previously reported in one patient with similar clinicopathologic features. It is suggested that i(7q) is a primary, nonrandom chromosomal abnormality in hepatosplenic T γ/δ PTL.
Deletion of chromosome arm 17p dna sequences in pediatric high‐grade and juvenile pilocytic astrocytomas
Authors: Willert Jennifer R. , Daneshvar Laleh , Sheffield Val C. , Cogen Philip H.
Published: February 2007

In adults, loss of heterozygosity for DNA on 17p has been shown in high‐grade anaplastic astrocytomas (AAs) and glioblastomas multiforme (GMs), and mutation of the TP53 tumor suppressor gene has been reported in all grades of astrocytomas. Little is known, however, about 17p deletion and TP53 mutation in juvenile pilocytic astrocytomas (JPAs), the most common low‐grade tumors seen in children. To elucidate the genetic characteristics of pediatric high‐grade astrocytomas and JPAs, we performed restriction fragment length polymorphism analysis with probes derived from 17p and TP53 mutational studies in 28 tumor specimens. Telomeric chromosome arm 17p markers 144‐D6 and ABR were lost in 6 (75%) of 8 informative tumors classified as high‐grade (7 AAs, 1 GM) and in 2 (10%) of 20 informative JPAs. Loss of 17p probes centromeric to the TP53 gene were also detected in 3 AAs and 5 JPAs. Four of the 6 (66%) JPAs with losses of 17p DNA sequences recurred rapidly despite aggressive therapy, whereas only 5 of the other 14 (36%) recurred. Mutation of the TP53 gene was detected by polymerase chain reaction and denaturing gradient gel electrophoresis in only 1 JPA and 1 AA. These tumors were also examined for MDM2 gene amplification as an alternate inactivation mechanism for TP53 gene function: no instances of alteration were identified. These results suggest that a gene or genes in addition to TP53 on 17p may be involved in the etiology or progression of high‐grade astrocytomas and aggressive JPAs in children. Further, molecular genetic studies may be an important supplement to current clinical and radiologic data in predicting the outcome and guiding the therapy of children with aggressive and malignant astrocytomas.
New translocation t(2;13)(p12;q34) and rearrangement of the MLL gene in a childhood leukemia cell line
Authors: Kees Ursula R. , Campbell Lynda J. , Ford Jette , Willoughby Michael L. N. , Peroni Susanne E. , Ranford Pamela R. , Garson O. Margaret
Published: February 2007

Here we report the case of a 7‐month‐old boy who presented with biphenotypic acute leukemia, but with leukemia cells of B‐cell phenotype present at the time of relapse. Two cell lines were derived from bone marrow specimens obtained at relapse, and immunophenotyping and analysis of antigen receptor gene configuration revealed concordance between the patient's leukemic cells and the cell lines. Cell line PER‐377 shows a new chromosomal abnormality, t(2;13)(p12;q34), a molecular rearrangement at chromosome band 11q23 in the absence of a cytogenetically detectable abnormality of this band, and deletion of the genes for IGK.
Identification of gains and losses of DNA sequences in primary bladder cancer by comparative genomic hybridization
Authors: Kallioniemi Anne , Kallioniemi Olli‐P. , Citro Gil , Sauter Guido , Devries Sandy , Kerschmann Russell , Caroll Peter , Waldman Fred
Published: February 2007

Comparative genomic hybridization (CGH) makes it possible to detect losses and gains of DNA sequences along all chromosomes in a tumor specimen based on the hybridization of differentially labeled tumor and normal DNA to normal human metaphase chromosomes. In this study, CGH analysis was applied to the identification of genomic imbalances in 26 bladder cancers in order to gain information on the genetic events underlying the development and progression of this malignancy. Losses affecting 11p, 11q, 8p, 9, 17p, 3p, and 12q were all seen in more than 20% of the tumors. The minimal common region of loss in each chromosome was identified based on the analysis of overlapping deletions in different tumors. Gains of DNA sequences were most often found at chromosomal regions distinct from the locations of currently known oncogenes. The bands involved in more than 10% of the tumors were 8q21, 13q21‐q34, 1q31, 3q24‐q26, and 1p22. In conclusion, these CGH data highlight several previously unreported genetic alterations in bladder cancer. Further detailed studies of these regions with specific molecular genetic techniques may lead to the identification of tumor suppressor genes and oncogenes that play an important role in bladder tumorigenesis.
Concurrent presence of inv(14)(q11q32) and t(4;11)(q21;q23) in Pre‐B Acute Lymphoblastic leukemia
Authors: Chervinsky David S. , Grossi Mauro , Kakati Surabhi , Block Annemarie W. , Aplan Peter D.
Published: February 2007

The inv(14)(q11q32) is a non‐random chromosomal aberration which has been associated with a variety of T‐cell malignancies. We have studied a case of inv(14)(q11q32) that is unique in several respects. First, the inversion, which is expressed at the mRNA level, occurred in the context of a pre‐B acute lymphoblastic leukemia (ALL) as opposed to a T‐cell malignancy. Second, cloning and sequencing of the inversion revealed that it resulted from a fusion between an immunoglobulin heavy chain variable (V) segment and a T‐cell receptor delta diversity (D) segment. In addition, the patient had a second chromosomal abnormality at diagnosis, a t(4;11)(q21;q23) which disrupted the MLL gene. The fact that there were two distinct chromosomal abnormalities at diagnosis enabled us to address the question of leukemic clonal evolution during the course of this patient's disease. We present evidence suggesting that the t(4;11)(q21;q23) occurred first, with the inv(14)(q11q32) occurring as a second event.
Spontaneous loss of ph chromosome with maintenance of clonal hemopoiesis in an untreated patient with myeloproliferative disease and a long survival
Authors: Luppi Mario , Morselli Monica , Emilia Giovanni , Temperani Paola , Marasca Roberto , Barozzi Patrizia , Selleri Licia , Torelli Giuseppe
Published: February 2007

The unusual case of myeloproliferative disease described here is characterized by the following features: (1) a clinically completely silent course for 11 years without splenomegaly, marrow fibrosis, or cellular morphologic alterations; (2) the presence, at the onset, of a Philadelphia (Ph) chromosome without DNA breakpoints in the M‐bcr region; (3) the spontaneous loss of detectable Ph‐positive cells, 5 years after the first finding of leukocytosis, in the absence of any therapy; (4) the maintenance of the clonal nature of hematopoiesis, as revealed by the PGK X‐linked inactivation pattern, in the absence of the Ph chromosome; and (5) a biphasic trend in the levels of leukocytes, red cells, and platelets during the years of observation.
An Alu VpA Marker on chromosome 1 demonstrates that replication errors manifest at the adenoma‐carcinoma transition in sporadic colorectal tumors
Authors: Young Joanne , Searle Jeffrey , Buttenshaw Ron , Thomas Lesley , Ward Michael , Chenevix‐Trench Georgia , Leggett Barbara
Published: February 2007

Widespread mutations in simple tandemly repeated (STR) DNA sequences are frequently found in colorectal tumors from patients with hereditary non‐polyposis colorectal cancer (HNPCC) and less frequently in sporadic colorectal cancers. The aims of this study were to determine the type of DNA sequence most commonly affected by such mutations and to examine the point in the natural history of the tumor where replication errors (RERs) appear. An unselected series of colorectal tumors (49 adenomas and 108 carcinomas) was examined with 4 different STR markers: one Alu VpA polymorphism (MYCL1), one tetranucleotide repeat (D17S846), one dinucleotide repeat (D3S1029), and one polyA repeat (APΔ3Δ). All 3 positive adenomas and 18 of 20 positive carcinomas showed replication errors in the Alu VpA sequence at the MYCL1 locus, making this marker more than twice as sensitive as the best of the other 3 markers. Importantly, all positive adenomas showed small foci of carcinoma in situ. This suggests that replication errors manifest at the adenoma/carcinoma transition in sporadic colorectal tumors.
Two tumor suppressive loci on chromosome 10 involved in human glioblastomas
Authors: Steck Dr.Peter A. , Ligon Azra Hadi , Cheong Paul , Yung W. K. Alfred , Pershouse Mark A.
Published: February 2007

A number of cytogenetic and molecular analyses have revealed very frequent and extensive losses of regions of chromosome 10 in human glioblastomas. Our recent studies have demonstrated that the transfer of a chromosome 10 into human glioblastoma cells resulted in suppression of their transformed and tumorigenic phenotype. To localize the suppressive region further, we isolated and characterized certain hybrid cells that had undergone chromosomal rearrangements to yield hybrid cells retaining only various regions of the inserted chromosome 10. One series of subclones showed the loss of the majority of the long arm of chromosome 10 (10q21‐10qter) and regained the ability to grow under anchorage‐independent conditions, but the cells still failed to exhibit significant tumorigenicity in nude mice. Another set of subclones exhibited major deletions of large segments of the long arm of chromosome 10 (10q21‐q23; 10q26‐qter), yet retained certain distal alleles associated with 10q24 to 10q26. These subclones were identical in their biological characteristics to the hybrids containing an intact chromosome 10, exhibiting no growth in soft agarose or in nude mice. These results implicate the presence of two independent phenotypically suppressive regions on chromosome 10 (10pter‐q11 and 10q24‐q26) that are involved in glioma progression.
Electrophoretic isolation of extrachromosomal DNA from tumor cells
Authors: Vandevanter Donald R. , Tseng John C.‐H. , Yirdaw Getachew
Published: February 2007

Gene amplification allows transformed cells to overexpress specific genes and gain a survival advantage. For this reason, cloning and characterization of amplified genes can improve our understanding of the biology of transformed cells. The techniques of in‐gel renaturation and chromosome microdissection can enrich for amplified DNA sequences, but both are labor intensive and have other drawbacks. We have developed an alternative strategy of enriching for amplified DNA sequences that involves two‐directional agarose gel electrophoresis of extrachromosomal circular DNA. Extrachromosomal circles can be detected with repetitive DNA probes and can be used to produce DNA probes suitable for fluorescence in situ hybridization for location of genomic origin. The ability to enrich for amplified DNA without specialized equipment or transformed cell metaphases should prove useful in the search for new genes which are important in tumor cell progression.
DNA‐repeat instability is associated with colorectal cancers presenting minimal chromosome rearrangements
Authors: Remvikos Yorghos , Vogt Nicolas , Muleris Martine , Salmon Rémy J. , Malfoy Bernard , Dutrillaux Bernard
Published: February 2007

The DNA‐repeat [(CA)n] instability of colorectal cancer cells was studied relative to our previously defined classification based on chromosome alterations. Of the 23 tumors analyzed, 13 belonged to the “monosomic” type (MT) characterized by simultaneous loss of chromosome 18 and chromosome arm 17p, and many structural rearrangements, 7 to the “trisomic” type (TT) with many chromosome gains but few rearrangements, and 3 had a normal karyotype (NT). (CA)n repeat sequences were examined on chromosomes 2, 5, 11, 13, 18, and 20. We found sequence alterations in 12 tumors at 1 or several loci, 9 of which (1/13 MT, 5/7 TT, and 3/3 NT) exhibited a typical shift in allele size defined as microsatellite instability. Furthermore, a single alteration was observed for the MT tumor, whereas one NT tumor displayed instability on two and all the other tumors on three or more loci. These results suggest an inverse relationship between the occurrence of chromosome structural rearrangements and microsatellite instability, providing another argument for the subdivision of colorectal cancers into groups of distinct oncogenic pathways.
Visualization of INT2 and HST1 Amplification in oral squamous cell carcinomas
Authors: Lese Christa M. , Rossie Karen M. , Appel Billy N. , Reddy Jaya K. , Johnson Jonas T. , Myers Eugene N. , Gollin Susanne M.
Published: February 2007

Oral squamous cell carcinoma (OSCC) develops along a multistep genetic pathway including loss of tumor suppressor genes and alteration of oncogenes. We characterized seven OSCC cell lines by classical and molecular cytogenetic analysis and fresh tumor and adjacent oral mucosa corresponding to three of the cell lines by molecular cytogenetics. We observed homogeneously staining regions (hsrs) in four of the seven cell lines, at 11q13 in three and at 11q23 and in an unidentified marker chromosome in the fourth. Amplification of band 11q13 occurs in 30–60% of head and neck squamous cell carcinomas. To determine whether INT2 and HST1, both located in band 11q13, are amplified in the tissues and cell lines and to confirm the chromosomal location(s) of the amplification, we used dual‐color fluorescence in situ hybridization (FISH) with DNA probes for these genes and the chromosome 11 centromere. We report chromosomal localization of INT2/HST1 amplification in OSCC. Coamplification of INT2 and HST1 was detected in the hsrs in cultured tumor cells from the four hsr‐containing tumors and in directly harvested tumor cells, which were available from only two of these tumors. Amplification was not present in tumors lacking hsrs or adjacent oral mucosa corresponding to any of the seven tumors. The observation of amplification in fresh tumor cells suggests that the amplification was present in the patients, may play a key role in the development and/or progression of OSCC, and is not due to karyotypic evolution in vitro. The absence of amplification in the adjacent mucosa suggests that 11q13 amplification is a relatively late event in OSCC tumorigenesis.
Molecular characterization of mar, a multiple aberration region on human chromosome segment 12q13‐q15 implicated in various solid tumors
Authors: van de Ven Dr.Wim J. M. , Schoenmakers Eric F. P. M. , Wanschura Sylke , Kazmierczak Bernd , Kools Patrick F. J. , Geurts Jan M. W. , Bartnitzke Sabine , Berghe Herman Van Den , Bullerdiek Jörn
Published: February 2007

Chromosome arm 12q breakpoints in seven cell lines derived from primary pleomorphic salivary gland adenomas were mapped by FISH analysis relative to nine DNA probes. These probes all reside in a 2.8 Mb genomic DNA region of chromosome segment 12q13‐q15 and correspond to previously published sequence‐tagged sites (STS). Their relative positions were established on the basis of YAC cloning and long range physical and STS content mapping. The 12q breakpoints of five of the cell lines were found to be mapping within three different subregions of the 445 kb DNA interval that was recently defined as the uterine leiomyoma cluster region of chromosome 12 breakpoints (ULCR12) between STS RM33 and RM98. All seven breakpoints appeared to map within the 1.7 Mb DNA region between STS RM36 and RM103. Furthermore, the chromosome 12 breakpoints of three primary pleomorphic salivary gland adenomas were also found to be mapping between RM36 and RM103. Finally, FISH analysis of two lipoma cell lines with 12q13‐q15 aberrations pinpointed the breakpoints of these to relatively small and adjacent DNA segments which, as well as those of two primary lipomas, appeared to be located also between RM36 and RM103. We conclude from the observed clustering of the 12q breakpoints of the three distinct solid tumor types that the 1.7 Mb DNA region of the long arm of chromosome 12 between RM36 and RM103 is a multiple aberration region which we designate MAR.
Loss of heterozygosity on 7q31 occurs early during breast tumorigenesis
Authors: Champème Marie‐Hélène , Bièche Ivan , Beuzelin Michèle , Lidereau Rosette
Published: February 2007

Although human breast tumorigenesis is associated with the accumulation of mutations both in oncogenes and in tumor suppressor genes, the identity of the genetic alterations that are critical in the early stages of the breast tumorigenic process remains obscure. A high frequency (27–41%) of loss of heterozygosity (LOH) occurrence has been shown at the MET locus on chromosome band 7q31 and this specific alteration is associated with poorer survival. Here, we report that restriction fragment length polymorphism (RFLP) analysis on 221 informative (heterozygous) primary breast tumors and 57 informative relapses (13 local recurrences and 44 distant metastases) revealed a similar frequency of 7q31 LOH as tumors progress from primary cancer to relapse, in marked contrast to other changes such as 11p15.5 LOH. This finding suggests that inactivation of a putative tumor suppressor gene located in 7q31 is a very early event in breast tumorigenesis. Our results also show that metastatic potential is an induced phenomenon that occurs at a relatively early stage, rather than a marker of tumor progression.
Fusion of the EWS Gene to a DNA segment from 9q22‐31 in a human myxoid chondrosarcoma
Authors: Gill Sandra , McManus Aidan P. , Crew A. Jayne , Benjamin Harry , Sheer Denise , Gusterson Barry A. , Pinkerton C. Ross , Patel Ketan , Cooper Dr.Colin S. , Shipley Janet M.
Published: February 2007

Southern blot analyses revealed a rearrangement of the EWS gene in a skeletal human myxoid chondrosarcoma. Interphase fluorescence in situ hybridization (FISH) studies, using cosmid clones F7 and G9 that flank the EWS locus on 22q12, confirmed the presence of this EWS gene abnormality. Cloning the rearranged EWS DNA fragment and mapping by FISH demonstrated that the EWS gene is joined to DNA sequences localised in 9q22‐31. These findings are consistent with previous cytogenetic reports of a recurrent t(9;22)(q22‐31;q11‐12) in the myxoid variant of chondrosarcoma and reveal involvement of the EWS gene in a fourth type of human sarcoma.
Deletion mapping of chromosome II in carcinoma of the bladder
Authors: Shaw Margaret E. , Knowles Margaret A.
Published: February 2007

Deletions of the short arm of chromosome II have been identified by both cytogenetic and molecular criteria in bladder and other types of solid tumor, indicating the presence of one or more suppressor loci in this region. To localize the II p deletion target(s) more precisely and to screen for loss of heterozygosity (LOH) on the long arm of the chromosome, I00 bladder tumors were analyzed for LOH on chromosome II using restriction fragment length polymorphism (RFLPs) and microsatellite markers mapped to both II p and II q. Thirty‐four tumors were found to have LOH at I or more loci. Of these, I7 had LOH restricted to II p, I3 had LOH of both II p and II q, and 4 had LOH of II q only. Eight tumors showed LOH at all informative loci indicating probable loss of an entire copy of chromosome II. A common region of deletion was defined on II p between DIIS922(IIpI5.5) and DlIS569 (IIpI5.I‐I5.2). This region does not include the HRAS or WTI loci (at IIpI5.5and IIp13, respectively). Seventeen tumors had LOH on II q, 4 of which had LOH on II q only. The common region of deletion on II q was between FGF3 and DI IS490 (IIq I3‐q23.2). Two tumors showed LOH on both II p and II q with a clear region of retention of heterozygosity between, indicatinn the existence of two deletion targets on chromosome II. © 1995 Wiley‐Liss, Inc.
Frequent loss of chromosome arm Ip DNA in parathyroid adenomas
Authors: Cryns Vincent L. , Yi Su Min , Tahara Hideki , Gaz Randall D. , Arnold Andrew
Published: February 2007

Two molecular defects have been described in parathyroid adenomas: rearrangement and overexpression of the PRADI/cyclin DI oncogene and allelic loss of chromosome II DNA, often including the multiple endocrine neoplasia type I (MENI) putative tumor suppressor gene region. In an effort to identify additional parathyroid tumor suppressor genes, we examined 25 parathyroid adenomas for tumor‐specific allelic loss of polymorphic DNA loci located near known or candidate tumor suppressor genes. Control leukocyte DNA from all 25 patients was heterozygous for I or more of the 9 chromosome I markers examined. Allelic loss at I or more of these informative loci on chromosome I was observed in 10 of 25 (40%) adenomas. Although many tumors lost extensive regions on chromosome I, all but one of these tumors had allelic loss of distal I p (I p32‐pter); four tumors also lost loci on Iq. Allelic loss at IIqI3, the site of the MEN I gene, was detected in 5 of 2I (24%) informative cases, including 3 with Ip loss. In contrast, allelic loss was rarely observed at loci on 99 and Iop and was not observed at loci on 3p, 3q. 4p, 5q, I2q, I4q, I8q, 22q, or Xp. In summary, clonal allelic loss of loci on chromosome arm Ip is a frequent feature of parathyroid adenomas, implying that inactivation of a tumor suppressor gene(s) on Ip commonly contributes to their pathogenesis. © 1995 Wiley‐Liss, Inc.
Identification of two transcripts of AMLI/ETO‐fused gene in t(8;21) leukemic cells and expression of wild‐type ETO gene in hematopoietic cells
Authors: Era Takumi , Asou Norio , Kunisada Takahiro , Yamasaki Hiroshi , Asou Hiroya , Kamada Nanao , Nishikawa Shin‐Ichi , Yamaguchi Kazunari , Takatsuki Kiyoshi
Published: February 2007

The t(8; 21) is a common chromosomal abnormality, preferentially associated with acute leukemia showing features of myeloid differentiation. Recently, two genes–AMLI which has a unique runt domain, and ETO (MTG8)–have been isolated from the chromosomal breakpoint. In this study, we isolated and identified two fused transcripts from a leukemic cell line carrying t(8; 21). AMLI and ETO were fused at the same position in these transcripts. One of the transcripts codes a unique domain, including two zinc finger domains and three proline‐ and one leucine‐rich region. The other transcript codes only for one proline‐ and leucine‐rich region but lacks zinc finger domains. We demonstrated by polymerase chain reaction (PCR) analysis that I) these two transcripts are consistently expressed in leukemic cells with t(8; 21) obtained from patients and 2) expression of AMLI was not restricted to the particular stage of hematopoietic differentiation but was present in all hematopoietic cells investigated. We also provide evidence that two wild types of ETO transcripts containing the region of the ETO gene in fused transcripts are expressed in hematopoietic cells from different lineages. The widespread expression of AMLI and ETO in hematopoietic cells suggests a fundamental role of these proteins in hematopoiesis. Furthermore, the differences in the carboxy termini of ETO may modulate the activity of fused proteins resulting from the chromosomal translocation t(8; 21). © 1995 Wiley‐Liss, Inc.
Characterization of add(I)(p36) in non‐hodgkin lymphomas by fluorescence in situ hybridization
Authors: Bajalica Svetlana , Brøndum‐Nielsen Karen , Sørensen Anne‐Grethe , Pedersen Niels Tinggaard , Kristoffersson Ulf , Åkerman Måns , Anderson Margareta , Pisa Pavel , Nordenskjöld Magnus
Published: February 2007

Chromosome rearrangements involving chromosome I, band p36, are among the most common aberrations in non‐Hodgkin lymphomas (NHL). We have studied nine cases of NHL with add(I)(p36) using fluorescence in situ hybridization (FISH) from a series of 205 cases. Five were follicular low‐grade NHL and four were follicular or diffuse high‐grade NHL. Three of the five cases with follicular low‐grade NHL did not contain the 14; 18 translocation. The extra material on the add(l)(p36) in these three cases was derived from chromosome segment 2q31‐qter; in one it was observed as a sole clonal rearrangement. In the two remaining cases, with t(14; 18), the add(l)(p36) consisted of material from chromosome arms 3q and 17q, respectively. In the four cases of high‐grade NHL, the material added on to I p36 was derived from chromosomes 6, 9, 17, and 19, respectively. Using a I p36‐specific probe, DIS94, we showed a deletion on the add(I) in one of the cases with low‐grade NHL, whereas no loss was observed in one of the cases with high‐grade NHL. Our study indicates that cytogenetically similar add(l)(p36) are found in both high‐ and low‐grade NHL, and the breakpoint on Ip36 as well as the origin of translocated material may vary. © 1995 Wiley‐Liss, Inc.
Human chromosome II inhibits tumorigenicity of a murine squamous cell carcinoma cell line
Authors: Zenklusen Jean C. , Oshimura Mibuo , Barrett J. Carl , Conti Claudio J.
Published: February 2007

Loss of heterozygosity (LOH) of mouse chromosome 7 has been consistently demonstrated in chemically induced murine squamous cell carcinomas (SCCs). The region of this chromosome presenting LOH in the mouse tumors is syntenic to human chromosome segments II p I5 and II q. To determine whether the introduction of human chromosome (Hchr) II can suppress the growth of murine SCC, we injected four clones of a chemically induced murine SCC cell line bearing an Hchr II into athymic BALB/c nude mice. All microcell hybrid clones with Hchr II (CH721Hchr II) had latency periods twice as long as those of the parental CH72 cells and control hybrids containing a Hchr 12. Tumor‐derived cells from CH721Hchr II hybrids had lost centromeric and telomeric sequences from Hchr II. All repressed cell lines grew significantly m e slowly in vitro than did the controls. These results suggest that Hchr II contains a tumor‐suppressor gene capable of inhibiting tumorigenicity in chemically induced SCC, confirming common pathways in the development of human neoplasias and the murine model. © 1995 Wiley‐Liss, Inc.
Loss of neurofibromatosis type I (NFI) gene expression in pheochromocytomas from patients without NFI
Authors: Gutmann David H. , Geist Robert T. , Rose Kamala , Wallin Goran , Moley Jeffrey F.
Published: February 2007

The neurofibromatosis type 1 (NFI) gene encodes a tumor‐suppressor protein termed neurofibromin, which, in adults, is expressed predominantly in neurons, Schwann cells, and the adrenal medulla. Loss of NFI gene expression has been reported in Schwann cell tumors (neurofibrosarcomas) from patients with NF1 as well as in malignant melanomas and neuroblastomas from patients without NF1. Previously, we demonstrated the lack of neurofibromin expression in six pheochromocytomas from patients with NF1, supporting the idea that neurofibromin might be an essential regulator of cell growth in these cells. To determine whether NFI gene expression is similarly altered in pheochromocytomas from patients without NF1, we examined 20 pheochromocytomas for the presence of NFI RNA and neurofibromin by reverse‐transcribed polymerase chain reaction (RT‐PCR) and immunohistochemistry, respectively. Reduced or absent NFI gene expression was documented in 7 of these 20 tumors (35%) including 1 of 4 sporadic tumors, 3 of 10 tumors from patients with multiple endocrine neoplasia (MEN) 2A, 2 of 4 tumors from patients with MEN2B, and 1 of 2 tumors from patients with von Hippel‐Lindau syndrome. In addition, most of these tumors expressed predominantly the type 1 NFI isoform (75% type 1 NFI isoform expression) as opposed to other neural crest‐derived tissues such as adrenal gland and Schwann cells, which express predominantly type 2 NFI. This type 1 isoform predominance was also observed in the rat pheochromocytoma PC 12 cell line, suggesting that this change in isoform expression may be associated with the genesis of these tumors. These results collectively demonstrate that loss of NFI gene expression is associated with progression to neoplasia in tumors originating from neural crest‐derived cells in patients without clinical manifestations of neurofibromatosis, and they support the notion that neurofibromin is a tumor‐suppressor gene product involved in the pathogenesis of a wide variety of tumor types. © 1995 Wiley‐Liss, Inc.
Characterization of a t(I0; II) (pI3‐I4; qI4‐2I) in the monoblastic cell line U937
Authors: Shipley Janet , Williams Sarah , O'Byrne Anne , Kearney Lyndal , Jones Tania , Young Bryan , Dyer Martin , Catovsky Daniel , Sheer Denise , Gusterson Barry
Published: February 2007

Previous analysis of the monoblastic cell line U937 has shown that several sublines contain a rearranged chromosome arm I I q. In order to determine the true nature of the rearrangement, fluorescence in situ hybridization (FISH) was carried out with various combinations of single copy anonymous markers, clones containing genes, a chromosome 10 paint, and an I I centromere specific sequence. The rearrangement was deduced to be a reciprocal translocation between chromosomes 10 and 11 described as t( 10; 11 )(p 13‐ 14;q 14‐21 ). The breakpoint on chromosome 11 is telomeric to the /NT2 gene and the pHS11 probe at 11 q 13, and centromeric to the marker D 11536 localized to 11q 14.3‐q22. 1 and the MLL gene at 11 q23. Similar translocations have been reported in various acute leukemias, principally of the monocytic lineage, and also in T‐cell precursor acute lymphocytic leukemias. Further characterization of the genetic rearrangements in U937 may lead to the isolation of genes important in leukemogenesis and provide an in vitro system for their study. © 1995 Wiley‐Liss, Inc.
Loss of heterozygosity on the short arm of chromosome 3 in sporadic, von hippel‐lindau disease‐associated, and familial pheochromocytoma
Authors: Zeiger Martha A. , Zbar Berton , Keiser Harry , Linehan W. Marston , Gnarra James R.
Published: February 2007

Pheochromocytomas occur sporadically and are associated with several dominantly inherited cancer syndromes, including von Hippel‐Lindau (VHL) disease. We examined 14 pheochromocytomas (four from VHL patients, nine from sporadic patients, and one from a patient with familial pheochromocytoma) for loss of heterozygosity on chromosome arm 3p by using the polymerase chain reaction and restriction fragment length polymorphisms at eight loci. Loss of heterozygosity was detected in 8 of 14 pheochromocytomas examined: in three of the four VHL‐associated tumors, in four of the nine sporadic tumors, and in the familial pheochromocytoma‐associated tumor. Deletion of the inherited wild‐type VHL allele was demonstrated in both informative VHL‐associated pheochromocytomas, demonstrating involvement of VHL in pheochromocytoma development. However, because VHL mutations have not been detected in sporadic pheochromocytomas, VHL and/or another chromosome arm 3p gene may be involved in the etiology of these tumors. © 1995 Wiley‐Liss, Inc.
Accumulation of genetic changes during development and progression of hepatocellular carcinoma: Loss of heterozygosity on chromosome arm Ip occurs at an early stage of hepatocarcinogenesis
Authors: Kuroki Tamobu , Fujiwara Yoshiyuki , Tsuchiya Eiju , Nakamori Shouji , Imaoka Shingi , Kanematw Takashi , Nakamura Yusuke
Published: February 2007

To investigate cumulative genetic changes during development and progression of hepatocellular carcinoma (HCC), we examined DNAs isolated from I04 tumors for loss of heterozygosity (LOH) at I 3 loci on six chromosomal arms and for an increase of copy number (“multiplication”) of alleles on 8q, using polymorphic microsatellite markers. A comparison of genetic features with clinicopathological stages of these tumors revealed that LOH on I p had occurred in tumors at an early stage or with a well‐differentiated histological phenotype (8/26 31 %) as well as in tumors at more advanced stages. Genetic alterations on chromosome arms 4q. 8p, 8q, I 3q, I6q, and I7p were more often observed in tumors of more advanced stages and poorer differentiation grades. When size was the criterion for comparison, LOH on I p was observed frequently even in tumors smaller than 2 cm (6/16; 38%), whereas allelic losses on 16q were detected frequently only in larger tumors. These results suggest that the putative tumor suppressor gene(s) assumed to be located on I p may be involved in an early step of carcinogenesis in liver tissue and that the other genetic alterations examined here may play important roles in progression of HCC. © 1995 Wiley‐Liss, Inc.
Molecular, cytogenetic, and phenotypic studies of a constitutional reciprocal translocation t(5; I0)(q22; q25) responsible for familial adenomatous polyposis in a Dutch pedigree
Authors: Van Der Luijt Rob B. , Tops Carli M. J. , Khan P. Meera , Van Der Klift Heleen M. , Breukel Cor , Van Leeuwen‐Cornelisse Inge S. J. , Dauwerse Hans G. , Beverstock Geoffrey C. , Van Noort Ellen , Snel Pleun , Slors Frederik J. M. , Vasen Hans F. A. , Fodde Riccardo
Published: February 2007

Familial adenomatous polyposis (FAP) is an inherited predisposition to colorectal cancer caused by germline mutations in the adenomatous polyposis coli (APC) gene located on chromosome segment 5q21‐q22. We detected a germline rearrangement of the APC gene in a Dutch FAP family by screening genomic DNA samples with APC cDNA probes. Subsequent molecular and cytogenetic studies revealed a constitutional reciprocal translocation t(5; 10) (q22; q25) that resulted in the disruption of the APC gene. Southern blot and polymorphic marker analysis indicated that part of the APC gene had been deleted. Analysis of the APC protein product indicated that the translocation breakpoint did not lead t o the formation of a detectable truncated APC protein but apparently resulted in a null allele. Evaluation of the clinical phenotypes in the patients suggested that they exhibited features of an unusual form of FAP characterized by a slightly delayed age of onset of colorectal cancer and a reduced number of colorectal polyps. The latter were mainly sessile and were located predominantly in the proximal colon. To our knowledge, this is the first description of FAP caused by a reciprocal translocation disrupting the APC gene. © 1995 Wiley‐Liss, Inc.
A new cytogenetic subgroup in uterine leiomyoma is characterized by a deletion of the long arm of chromosome 3
Authors: Cin Paola Dal , Moerman Philippe , Deprest Jan , Brosens Ivo , Berghe Herman Van Den
Published: February 2007

Our cytogenetic findings in 175 uterine leiomyomas revealed 52 tumors with clonal chromosome abnormalities, eight of which did not belong to any well‐delineated cytogenetic abnormal subgroup. However, an interstitial deletion of the long arm of chromosome 3 was found, as the sole chromosome abnormality, in three cases. We believe that this involvement of 3q is significant enough to consider it as a new cytogenetic subgroup of uterine leiomyoma. © 1995 Wiley‐Liss, Inc.
Loss of heterozygosity on the X chromosome in human breast cancer
Authors: Loupart Marie‐Louise , Adams Susan , Armour John A. L. , Walker Rosemary , Brammar William , Varley Jennifer
Published: February 2007

The analysis of loss of heterozygosity (LOH) in tumours can be a powerful tool for mapping the sites of tumour suppressor genes in the human genome. A panel of breast cancer patients was assembled as pairs of tumour and lymphocyte DNA samples and LOH studies carried out by Southern hybridisation with polymorphic loci mapping to the X chromosome with appropriate controls. Deletion mapping revealed a high frequency of small regionalised deletions, defining at least three independent regions, one of which is particularly well mapped to a 500 kb stretch of DNA in the distal portion of the pseudoautosomal region of Xp. A second region has been identified within the pseudoautosomal region close to the pseudoautosomal boundary, and there is a third discrete site of loss on distal Xq. Perturbations of sequences at these regions represent independent events in a number of patients. This study represents the first detailed analysis of LOH on the X chromosome in human breast tumours, the results of which indicate that at least three regions of this chromosome are involved in the disease. © 1995 Wiley‐Liss, Inc.
Cytogenetic studies of breast carcinomas: Different karyotypic profiles detected by direct harvesting and short‐term culture
Authors: Steinarsdóttir Margrét , Pétursdóttir Ingibjörg , Snorradóttir Steinunn , Eyfjörd Jórunn E. , Ögmundsdóttir Helga M.
Published: February 2007

Chromosome analysis was performed on samples from 85 consecutive patients with breast cancer by one or more of three different methods: direct harvest, culture after mechanical disaggregation, and culture after collagenase digestion. Metaphases suitable for karyotyping were obtained in 70% of the cases; direct harvest yielded metaphases in 29% and cultures without and with digestion in 40% and 59%, respectively. Chromosomal abnormalities were detected in 37 cases. Cells judged to be phenotypically abnormal in culture were twice as likely to reveal chromosomal aberrations as normal‐looking cells. Eight cases showed multiclonal abnormalities. Significant differences were detected in the karyotypic profile depending on the method used. With direct harvest, the yield of complex chromosomal changes was 87%, compared to 44% after culture of digested tissue (P < 0.01), and also polyploidy was more common in direct‐harvested samples. Detailed karyotypic analysis was possible in 29 primary tumors. The chromosomes most frequently involved were 1, 3, 7, 11, 16, and 17. Recurrent structural abnormalities were der( 1; 16) (q 10; p 10), i(1)(q10), del(6)(q21), and del(1)(p22). Breakpoints clustered to the cententromere regions of chromosomes 1, 3, 11, 15, and 16 and to the short arms of chromosomes 7, 17, and 19. Seven of twenty‐nine fully analyzed cases had a family history of breast cancer, and changes of chromosomes 1, 3, and 15 seemed to be more common in these cases. There was an association between karyotype and survival: The 3 year survival was 63% in patients with complex karyotypic changes and 92% in those without complex changes. © 1995 Wiley‐Liss, Inc.
Allelic imbalance in gastric cancer: An affected site on chromosome arm 3p
Authors: Schneider Barbara G. , Pulitzer Donald R. , Brown Rhonda D. , Prihoda Thomas J. , Bostwick David G. , Saldivar Victor , Rodriguez‐Martinez Hector A. , Gutiérrez‐Diaz C. M. Esther , O'Connell Peter
Published: February 2007

In order to detect regions of DNA containing tumor suppressor genes involved in the development of gastric cancer, we performed an allelotype study on 78 gastric adenocarcinomas from a population composed largely of Texan Hispanics and Anglos, two ethnic groups that have a ratio of incidence rates of gastric cancer of approximately 2: 1. In total, 42 microsatellite markers were employed, which detected at least one site per arm of each autosome in the human genome. These included several markers linked to known tumor suppressor genes (TP53, APC, DCC, RBI, and BRCAI). Sites showing quantitative allelic imbalance (Al) greater than 30% were located on 3p (36%), 11q (31%), 12q (38%), 13q (33%), 17p near TP53 (74%), and 17q near BRCAI (32%). Among the 22% of cases showing microsatellite instability (MI), a subset (4 of 17) showed instability at 59% or more of sites tested. No ethnic bias was detected in cases showing MI or in cases with Al at sites with rates of AI above 30%. Tumors of the intestinal subtype were significantly more likely than diffuse tumors to show AI at D 135170 (P = 0.01). A deletion map of chromosome arm 3p was prepared for tumors with Al at D3S1478. These data indicate that a tumor suppressor gene on chromosome arm 3p is involved in the development of a subset of gastric cancers. © 1995 Wiley‐Liss, Inc.
Molecular analysis of genetic changes in ependymomas
Authors: Bijlsma Emilia K. , Voesten Annet M. J. , Bijleveld Engelien H. , Troost Dirk , Westerveld Andries , Mérel Philippe , Thomas Gilles , Hulsebos Theo J. M.
Published: February 2007

Ependymomas are glial cell‐derived tumors. They are, in contrast to other gliomas (astrocytomas, oligodendrogliomas, and oligoastrocytomas), ill‐defined with respect to the genes and chromosomal segments important in their tumorigenesis. In this study, we extensively screened I7 ependymomas for genetic changes characteristic of other gliomas. Allelic loss was detected on chromosome arm 22q in three tumors; on chromosome 10 in two tumors; on chromosome arm 17p in two tumors; and on chromosome arms 6q, 9p, I 3q, and I9q, each in one tumor. No allelic losses were found on chromosome arms I p and I6q. None of the tumors had EGFR gene amplification. In each case, the chromosomal segment affected by the deletion included the region known t o harbor a tumor suppressor gene important in glioma tumorigenesis. We conclude that ependymomas resemble the other glial neoplasms with respect to type and location of the chromosomal changes involved. Given the relatively infrequent occurrence of these genetic changes, ependymomas should be considered genetically as low‐grade gliomas. © 1995 Wiley‐Liss, Inc.
Loss of Chromosome 17 loci in prostate cancer detected by polymerase chain reaction quantitation of allelic markers
Authors: Brothman Arthur R. , Steele Michael R. , Williams Briana J. , Jones Emma , Odelberg Shannon , Albertsen Hans M. , Jorde Lynn B. , Rohr L. Ralph , Stephenson Robert A.
Published: February 2007

Using a polymerase chain reaction/microsatellite marker system, we demonstrated that 6 of 22 (27%) clinical stage B (early) primary prostate tumors showed loss of heterozygosity at one or more of five loci on chromosome 17. The sensitivity of this study was increased by use of a Phosphorlmager and statistical analysis of replicate tumor‐normal DNA pairs. Two patients showed tumor‐specific interstitial loss at a locus in close proximity to the familial breast cancer gene BRCAI. These findings suggest that genes on the proximal long arm of chromosome I7 play a pivotal role in the early development of at least a subset of prostatic tumors. © 1995 Wiley‐Liss, Inc.
Loss of heterozygosity in the tuberous sclerosis (TSC2) region of chromosome band l6p13 occurs in sporadic as well as TSC‐associated renal angiomyolipomas
Authors: Henske Elizabeth Petri , Neumann Hartmut P. H. , Scheithauer Bernd W. , Herbst Eberhard W. , Short M. Priscilla , Kwiatkowski David J.
Published: February 2007

Angiomyolipomas (AMLs) are renal tumors that occur both sporadically and in association with tuberous sclerosis (TSC). TSC is an autosomal dominant disorder characterized by hamartomatous lesions in multiple organs. Two TSC loci are recognized TSCl on 9q34 and TSC2 on 16pl3. Loss of heterozygosity (LOH) at the TSCI and TSC2 loci in lesions from TSC patients has recently been reported. Lesions that are not associated with TSC have not been previously examined for LOH at the TSC loci. We analyzed 29 renal angiomyolipomas from patients without a history of TSC. Three tumors demonstrated LOH on I6p 13. This is the first report indicating that mutations in TSC2 occur in tumors of patients who do not have TSC. We also found LOH on I6p 13 in 5 of 8 TSC‐associated AMLs. Two of these tumors were from a single patient and demonstrated different regions of LOH. These findings support the hypothesis that the TSC2 gene functions as a tumor suppressor.