bluuebunny/crossref_metadata_2025 huggingface dataset:
Epithelial‐mesenchymal transitions during cell culture of primary thyroid tumors?
Authors: Herrmann Marille E. , Trevor Katrina T.
Published: February 2007

Fibroblast contamination of epithelial tumor cell cultures is of great concern when examining tumor cells in vitro for specific biochemical and cytogenetic changes. The observations of normal karyotypes in thyroid tumor cell cultures have raised the concern of whether residual tissue fibroblasts might obscure the cytogenetic analysis of transformed epithelial cells. We have characterized early passaged thyroid tumor cells to examine the proportions of epithelial and fibroblastic cell types. Cells were analyzed by immunocytology using antibodies recognizing the thyroid prohormone thyroglobulin, epithelial cytokeratins, and vimentin, a mesenchyme marker. Tumors consisted of one follicular adenoma and five papillary carcinomas. When examined by day 15 in culture, all cells contained filaments composed of vimentin, which most likely represents an adaptation to culture conditions. Double immunofluorescence staining for thyroglobulin and cytokeratin revealed the presence of not only epithelial but also spindle‐like fibroblastoid cells possessing thyroid epithelial cell markers. The results suggest that in thyroid tumor cultures there is a unique cell type intermediate between epithelial and mesenchyme phenotypes that must be considered when performing cytogenetic analysis. © 1993 Wiley‐Liss, Inc.
Clusters of chromosome 9 aberrations are associated with clinico‐pathologic subsets of non‐Hodgkin's lymphoma
Authors: Offit Kenneth , Parsa Nasser Z. , Jhanwar Suresh C. , Filippa Daniel , Wachtel Mitchell , Chaganti R. S. K.
Published: February 2007

In this study we analyzed nonrandom aberrations affecting chromosome 9 in a series of 426 consecutively ascertained, karyotypically abnormal non‐Hodgkin's lymphoma (NHL) tumors derived from 407 patients. Cytogenetic abnormalities were correlated with clinical, histologic, and immunologic features. Structural abnormalities of chromosome 9 were identified in 60 specimens derived from 59 patients. The recurring abnormalities among these were associated with 4 clinico‐pathologic subsets. The first comprised 7 cases of t(9;14)(p13;q32), 6 of which had small lymphocytic lymphoma, plasmacytoid subtype, and an indolent clinical course. The second group included 12 cases with breaks at 9q11–13 and diffuse lymphomas with a large‐cell component and a typical response to combination chemotherapy. The third group was comprised of 7 cases with 9q deletions, with a common deleted region encompassing 9q31–32. These cases were characterized by diffuse B‐cell histology, young age, and poor clinical outcome. The fourth subset included 5 intermediate‐ to high‐grade T‐cell tumors with breaks at 9q34. This analysis of chromosome 9 aberrations in NHL comprises the first such effort based on a large series of tumors. We identify and report here new clinico‐pathologic subsets with shared abnormalities of chromosome 9, which should facilitate new approaches to the analysis of the etiology and clinical behavior of NHL. © 1993 Wiley‐Liss, Inc.
Two‐color FISH characterization of i(1q) and der(1;16) in human breast cancer cells
Authors: Kokalj‐Vokac Nadja , Alemeida Anna , Gerbault‐Seureau Michèle , Malfoy Bernard , Dutrillaux Bernard
Published: February 2007

Two‐color fluorescent in situ hybridizations using probes for alphoid (α) and classical satellite (CS) DNAs from chromosomes 1 and 16 were performed to characterize i(1q), der(1;16), and complex rearrangements observed in breast cancer cells from fresh tumors and established cell lines. Six of seven i(1q) occurred after breakage in the α1 containing region and one of seven was dicentric, with breakage in 1p11.2. The five der(1;16)(q10;p10) studied appeared to result from a variety of breakpoints involving α1, α16, CS1, and CS16 DNAs. All had conserved α16 DNA, suggesting a segregation of the der(1;16) leading to a loss of 16q and a gain of 1q in most cases. One complex rearrangement of chromosome 1 also appeared to involve chromosome 16, suggesting that a der(1;16) occurred first, followed by another rearrangement. Both the apparent preferential involvement of constitutive heterochromatin harboring α and CS DNAs and the variety of breakpoints spanning along heterochromatin suggest that the important consequence of the rearrangement is not the breakage per se but the resulting imbalance. © 1993 Wiley‐Liss, Inc.
Molecular deletion of 9p sequences in non‐small cell lung cancer and malignant mesothelioma
Authors: Center Rob , Lukeis Robyn , Dietzsch Erin , Gillespie Matthew , Garson O. Margaret
Published: February 2007

Previously we have reported non‐random cytogenetic abnormalities involving the short arm of chromosome 9 (9p) in the majority of primary non‐small cell lung cancer (NSCLC) patient samples, which indicated loss of DNA sequences. In another lung tumor, pleural malignant mesothelioma (MM), cytogenetic changes also include apparent deletions of 9p. To define the location and extent of deletions of 9p in NSCLC and MM, Southern blot analyses on six NSCLC and five MM cell lines using molecular probes to 9p loci (IFNA, IFNBI, D9S3, and D9S19) were performed, and DNA dosage was determined by densitometry. Our data demonstrated reduced dosage of 9p sequences in three of six NSCLC and four of five MM lines. A homozygous deletion of D9S3 was found in one NSCLC and one MM cell line. The region of common loss overlapped the D9S3 locus and was flanked by the IFNBI and D9S19 loci. IFNBI has previously been localized to 9p22, and the D9S3 and D9S19 loci have been mapped in this study by in situ hybridization to 9p21 and 9p13, respectively. We hypothesize the existence of one or more tumor suppressor genes on 9p with a role in the development or progression of NSCLC and MM. © 1993 Wiley‐Liss, Inc.
Amplification of the 11q13 region in human carcinoma cell lines: A mechanistic view
Authors: Roelofs Helene , Schuuring Ed , Wiegant Joop , Michalides Rob , Giphart‐Gassler Micheline
Published: February 2007

We previously proposed that a local duplication, not the loss of the subsequently amplified marker from its original site, might be the first step in gene amplification in human cells. It is important to investigate this issue in naturally occurring amplification and when copy numbers are relatively low. We have examined the location of single‐copy and amplified 11q13 sequences in cell lines from human breast cancers and squamous cell carcinomas using fluorescence in situ hybridization both with a probe specific for the 11q13 amplifying region and with a chromosome 11‐specific library. We show that in most cell lines the 11q13 amplicons are physically linked to chromosome 11 or to a chromosome derived from chromosome 11 by various rearrangements near the 11q13 region. In none of the cell lines were interstitial deletions of 11q13 detected. These results indicate that 11q13 amplification in human tumor cells generally does not involve deletion as the initial step. One cell line with chromosomally located amplified 11q13 sequences contained double minutes that harbored the MYC gene but no 11q13 sequences. This suggests that the genetic outcome and the mechanism of gene amplification are probably dependent on specific DNA sequences rather than on the origin of the cells. © 1993 Wiley‐Liss, Inc.
PRAD1/lCyclin D1 proto‐oncogene: Genomic organization, 5′ dna sequence, and sequence of a tumor‐specific rearrangement breakpoint
Authors: Motokura Toru , Arnold Andrew
Published: February 2007

PRAD1 (previously D11S287) is a putative proto‐oncogene at 11q13, activated by overexpression through gene rearrangement or gene amplification in several types of human tumors including parathyroid adenomas, centrocytic lymphomas and other B‐cell tumors with t(11;14), and breast cancers. PRAD1 (also CCND1) encodes cyclin D1, which may regulate the G1‐S phase transition in the cell cycle. Here, we report the cloning and characterization of the chromosomal PRAD1/cyclin D1 gene and the sequence of its promoter region. The gene spans about 15 kb and has 5 exons; its promoter region has Sp 1 binding sites and no obvious TATA box, characteristics of housekeeping genes and growth‐regulating genes. Furthermore, an E2F binding motif present close to the major transcription start site may be involved in cell cycle‐dependent expression of this gene. We also report the sequence of DNAs spanning joining regions of a reciprocal parathyroid hormone/PRAD1 gene rearrangement in a parathyroid adenoma. Comparison with normal sequences suggests that the rearrangement was not a simple break‐and‐ligate event, but rather involved multiple steps, including two microdeletions and a microinversion. Very short sequences conserved near the breakpoints and symmetrical elements in the eventually inverted DNA segment might have played a role in this illegitimate complex recombination, which may have similarities with a constitutional translocation in Duchenne muscular dystrophy. © 1993 Wiley‐Liss, Inc.
Consistent chromosomal anomalies in keratinocyte cell lines derived from untreated malignant lesions of the oral cavity
Authors: Patel Vyomesh , Yeudall W. Andrew , Gardner Anne , Mutlu Serdar , Scully Crispian , Prime Stephen S.
Published: February 2007

Cytogenetic analysis has been carried out on 8 early passage cell lines derived from 8 untreated human oral squamous cell carcinomas. Clonal aberrations were detected in the karyotypes of each cell line. A high frequency of breakpoints were noted on chromosomes 1, 7, 8, 9, 11, and X. An isochromosome 8 was present in 6 out of 8 cell lines; isochromosome 9 (3 cell lines) and isochromosome 11 (1 cell line) were also found. In 4 out of 8 cell lines the X chromosome harboured breakpoints, a novel finding in oral squamous cell carcinomas. Breakpoints were common on chromosome 1, with 1p12–p13 most frequently involved. Tandem duplication of 11q13–q23, which contains a number of growth regulatory genes, was also noted in 2 cases. We correlate the sites of proto‐oncogenes and other growth control genes with chromosomal breakpoints and suggest that several of these may play a role in the pathogenesis of oral cancer. © 1993 Wiley‐Liss, Inc.
Use of fluorescence in situ hybridization for retrospective detection of aneuploidy in multiple myeloma
Authors: Lee Wonbae , Han Kyungja , Drut Rosa M. , Harris Charles P. , Meisner Lorraine F.
Published: February 2007

In malignancies with a low mitotic index such as multiple myeloma (MM), conventional cytogenetic studies may not be informative. This study's purpose was to assess specific numerical chromosomal aberrations in non‐dividing MM cells by fluorescence in situ hybridization (FISH) of DNA chromosome probes on bone marrow smears. Old air‐dried bone marrow smears from 18 MM patients were probed with alpha satellite DNA sequences for chromosomes 7, X, and Y, and a whole painting probe for chromosome 11. Plasma cells were identified by their morphologic characteristics so that counts of fluorescent signals in the nuclei of MM cells could be differentiated from those of normal marrow cells. Numerical chromosome aberrations were found in 66.7% of the cases (12 of 18), including 5 cases of trisomy 7, 2 cases of tetraploidy, 2 cases of monosomy X in females, 2 cases of disomy X in males, and 1 case of nullisomy Y. In addition, 2 of the 7 cases probed with chromosome 11 paint demonstrated 3 signals in about 15% of the cells. This study illustrates the advantages of FISH for interphase analysis of chromosome aberrations in slowly dividing cells, as well as the ability to use old slides for retrospective studies. © 1993 Wiley‐Liss, Inc.
Clonal cytogenetic evolution in a squamous cell carcinoma of the skin from a xeroderma pigmentosum patient
Authors: Worsham Maria J. , Carey Thomas E. , Benninger Michael S. , Gasser Kathleen M. , Kelker Wolfgang , Zarbo Richard J. , van Dyke Daniel L.
Published: February 2007

Cytogenetic changes in epithelial neoplasms are often complex, making it difficult to determine which are the primary abnormalities and which are secondary. In this report, we describe clonal evolution in a cytogenetically simple, but clinically aggressive squamous cell cancer of the skin from a patient with xeroderma pigmentosum. Chromosome preparations were analyzed from a direct harvest, three independent primary harvests, and passaged cell lines. Three closely related tumor subclones were identified in the primary cultures, and all three proliferated in vitro. Monosomy 4 and a chromosome 9 rearrangement were present in all three subclones and monosomy 21 was present in two subclones. An i(9p) and an i(9q) were derived from the same chromosome 9, and there was concurrent loss of the homologous chromosome 9. In addition, each subclone was characterized by a further specific evolutionary change: t(5;7) (q11.2;p22) in subclone 1, der (11)t(10;11) (q21;p14) in subclone 2, and der (14)t(13;14) (q14;q32) in subclone 3. All three subclones were represented by hypodiploid and hypotetraploid metaphases. Loss of chromosomes from hypotetraploid cells and an 11q+ were the only other changes found in this tumor. The early genetic events in the evolution of this squamous cell cancer, monosomy 4, i(9p), i(9q), and monosomy 21, represent loss of chromosome regions that are commonly lost in other squamous cell carcinomas of the head and neck region. Taken together, these observations indicate that genes on these chromosomal regions are probably important and possibly sufficient for the development of squamous cell carcinoma. © 1993 Wiley‐Liss, Inc.
Clonal chromosome abnormalities in human breast carcinomas II. Thirty‐four cases with metastatic disease
Authors: Trent Jeffrey , Yang Jin‐Ming , Emerson Julia , Dalton William , McGee Daniel , Massey Kathy , Thompson Floyd , Villar Hugo
Published: February 2007

Cytogenetic analysis was performed on a selected series of short‐term cultures from 34 patients with documented metastatic breast carcinoma. The majority of tumor cells were hyperdiploid, with clonal structural alterations observed in 94% of patients (32/34). The most common numeric changes were –2, –15, and –18. Chromosome 20 was the most frequently overrepresented (in near‐3n tumors only). Clonal structural chromosome alterations included isochromosomes, terminal deletions, and, most frequently, unbalanced non‐reciprocal translocations. Chromosomes most often involved in structural rearrangements included 1, 7, 11, and 6 (accounting for 24.7%, 10.3%, 9.1%, and 7.0% of breakpoints, respectively). When the breakpoints of clonal structural abnormalities were analyzed, they were shown to cluster to several chromosome segments, including 1p11‐q21, 7pter, 11p12‐q12, and 6q11–21. An analysis of the net gain or loss of specific chromosome segments was also performed, with the most consistent tendency observed being the over‐representation of 1q, 6p, 7, and 11. The most frequent losses included 1p, 6q, 7, and 11q. © 1993 Wiley‐Liss, Inc.
Preferential clustering of chromosomal breakpoints in Burkitt's lymphomas and L3 type acute lymphoblastic leukemias with a t(8;14) translocation
Authors: Saglio Giuseppe , Borrello Maria Grazia , Guerrasio Angelo , Sozzi Gabriella , Serra Anna , Celle Paola Francia Di , Foa Robin , Ferrarini Manlio , Roncella Silvio , Pignatti Caterina Borgna , Marradi Pierluigi , Izzo Pietro , Soler Jesus , Pierotti Marco
Published: February 2007

We have analyzed the type of MYC/IG heavy‐chain locus (IGH) rearrangement present in 15 patients affected by t(8; 14)‐positive primary Burkitt's lymphoma or acute lymphoblastic leukemia of the L3 type in an attempt to map in detail the locations of the chromosome 8 and chromosome 14 breakpoints. The almost constant position of the chromosome 8 breakpoint (within or immediately 5′ of the MYC gene) together with two distinct clusters of breakpoints on chromosome 14 resulted in two main types of MYC/IGH (present in 12 of 15 cases). In the first type (six cases), the MYC gene or at least its coding portion was joined with the JH region on chromosome 14, whereas in the second, present in another six cases, the MYC gene and the Cαl region were juxtaposed. Physical linkage between the translocated MYC and a known enhancer element of the IGH locus is the common feature in the two types of rearrangement, suggesting that a high‐level constitutive expression plays a prominent role in MYC activation. Interestingly, the chromosome 14 break site within the switch α1 region, which has been only occasionally described in other cases, is present in 40% of our patients, suggesting the existence of preferential breakpoint cluster regions in cases of similar geographic origin. © 1993 Wiley‐Liss, Inc.
Structural organization of MYCN amplicons of neuroblastoma tumors, xenografts, and cell lines characterized by the sequences encompassing the MYCN amplicons in a human neuroblastoma cell line
Authors: Akiyama Kiyotaka , Kanda Naotoshi , Yamada Masao , Kato Mieko , Tadokoro Keiko , Matsunaga Tadashi , Nishi Yoshisuke
Published: February 2007

We characterized differences in the structural organization of the MYCN amplicons of a number of neuroblastomas by analyzing 8 contigs spanning 330 kb cloned from the MYCN amplicon of a neuroblastoma cell line. Some regions were amplified in almost all specimens, the conserved regions (CRs), and others were differentially amplified in some subsets, the non‐conserved regions (NCRs). CRs constituted only 20% of the 330 kb region, with the remainder being NCRs. The regions that inevitably co‐segregate with the MYCN gene make up the core, whereas flanking regions are retained at random. If a histogram of the frequency with which the amplified NCR sequences from one specimen match those of the cell line MC‐NB‐1 shows a random distribution, the NCRs would co‐segregate with MYCN as a result of random events. However, both the tumors and cell lines/xenografts showed a distribution with two distinct peaks; one from a group containing a small number of sequences with a fairly high degree of homology to the NCRs of MC‐NB‐1, and the other from a group containing a large number of sequences with little homology. These results indicate that the flanking segments are preferentially co‐segregated with MYCN by a non‐random mechanism. © 1993 Wiley‐Liss, Inc.
Regional fine mapping of the β crystallin genes on chromosome 22 excludes these genes as physically linked markers for neurofibromatosis type 2
Authors: Bijlsma Emilia K. , Delattre Olivier , Juyn Jenneke A. , Melot Thomas , Westerveld Andries , Dumanski Jan P. , Thomas Gilles , Hulsebos Theo J. M.
Published: February 2007

Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disease, characterized by the development of bilateral vestibular schwannomas. The NF2 gene has been assigned to chromosome 22. Cataract and other eye abnormalities are frequently seen in NF2 patients. The specific association of eye abnormalities and NF2 might be caused by a genetic change on chromosome 22 that affects both the NF2 gene and a physically linked crystallin gene. In order to test this hypothesis, we regionally localized the known crystallin genes (i.e. CRYBB2, CRYBB2P1, CRYBB3, and CRYBA4) on chromosome 22. Crystallin gene‐specific probes were hybridized to an extended panel of human x rodent somatic cell hybrids containing various portions of chromosome 22. It was found that all crystallin genes map to a very small region on chromosome 22 that is physically separate from the NF2 gene region by at least 160 kb of DNA. In addition, we found that the βB crystallin genes (CRYBB2, CRYBB2P1, and CRYBB3) are clustered on a 300 kb Sacll fragment and that the βA4 crystallin gene (CRYBA4) is not part of this cluster. We conclude that the ocular manifestations in many NF2 patients are probably not the primary consequence of rearrangements on chromosome 22 that involve both the NF2 gene and a nearby β crystallin gene.\\wiley5\wiley$\Wiley‐JWPH\final\jwph471
Cloning of a breakpoint cluster region at band 3q27 involved in human non‐Hodgkin's lymphoma
Authors: Deweindt Clotilde , Kerckaert Jean‐Pierre , Tilly Hervé , Quief Sabine , Nguyen Van Cong , Bastard Christian
Published: February 2007

In a previous cytogenetic analysis, we showed the recurrence of translocations involving band 3q27 and immunoglobulin gene regions in 20 out of 319 patients with non‐Hodgkin's lymphoma (NHL). We report here the molecular cloning of the translocation breakpoint from tumor cells of a patient (LAR) with t(3;14)(q27;q32) and the isolation of DNA probes which identify a major translocation cluster region (MTC) at band 3q27. A DNA library from LAR tumor cells was screened with a JH probe and several clones were identified corresponding either to a somatic rearrangement of JGH genes (V4‐D2‐J6‐Cμ clonal rearrangement) or to the t(3; 14). Analysis of the t(3; I 4) breakpoint showed that chromosome 3 material was translocated to an inverted 14q32 VH‐containing fragment which was itself translocated to the J3 gene. Chromosome 3‐assigned probes were used to investigate local DNA rearrangements in a series of NHL with 3q27 translocations. Rearrangements were detected in 13 of 17 patients including 9 of 11 with t(3;14)(q27;q32), I of 2 with t(2;3)(P12;q27), I of 2 with t(3;22)(q27;qII), and 2 of 2 NHL with translocations not involving an IG gene, namely, t(3;4)(q27;pII) and t(3;7)(q27;p12). The finding of this MTC should be useful for diagnostic and prognostic studies and for the identification of a novel oncogene at band 3q27 involved in the development of B cell NHL. © 1993 Wiley‐Liss, Inc.
Long‐range mapping of the 11q23 region involved in chromosome aberrations in human tumors by pulsed‐field gel electrophoresis with a yeast artificial chromosome
Authors: Akao Yukihiro , Tsujimoto Yoshihide , Seto Masao , Imai Takashi , Bergeron Dominique , Berbeau Benoit , Otsuki Yoshinori
Published: February 2007

We have previously demonstrated that the RCK gene involved in t(11;14)(q23;q32) and the more centromeric MLL/ALL1 gene involved in t(4;11)(q21;q23) and t(11;19)(q23;p13) are localized on different adjacent Notl fragments by using pulsed‐field gel electrophoresis (PFGE) analysis with the yeast artificial chromosome (YAC) clone yB22B2. The PFGE analysis using the YACs of YTY17 containing the prophobilinogen deaminase (PBGD), CBL2 and THY1 genes and yB22B2 allowed the following ordering of genes and breakpoints from CD3 to THY1 on 11q23: cent‐CD3‐ALL/MLL1‐RCK‐PBGD‐CBL2‐THY1, and the establishment of a long‐range restriction map covering these genes. In addition, we showed that the FLI1 region involved in the t(11;22)(q24;q12) in Ewing's sarcoma was more telomeric region than the THY1 gene by analyzing somatic cell hybrids carrying the 11q‐ and/or 14q+ chromosome of the t(11;14)(q23;q32) translocation, and by PFGE analysis of the YAC clone YTY17. © 1993 Wiley‐Liss, Inc.
Molecular cytogenetic analysis of i(12p)‐negative human male germ cell tumors
Authors: Rodriguez Eduardo , Houldsworth Jane , Reuter Victor E. , Meltzer Paul , Zhang Ji , Trent Jeffrey M. , Bosl George J. , Chaganti R. S. K.
Published: February 2007

The i(12p) chromosome has been shown to characterize more than 80% of male germ cell tumors (GCTs) and is an important diagnostic marker. Although recent cytogenetic analyses of GCTs have defined nonrandom chromosome abnormalities in these tumors, no attempt has so far been made to compare i(12p)‐positive and ‐negative tumors in terms of their cytogenetic, histologic, and clinical features. During a 5‐year period, we have ascertained 202 GCTs, of which 117 had clonally abnormal karyotypes. Among the latter, 91 had one or more copies of i(12p), whereas 26 lacked an i(12p). We report here the karyotypic analysis of these 26 i(12p)‐negative GCTs. In this group, nonrandom sites of chromosomal rearrangements included 12p13 (9/26) and 1p11‐q11 (5/26). Comparison of the cytogenetic features of i(12p)‐negative tumors with i(12p)‐positive tumors revealed the only significant difference to be rearrangements affecting 12p 13 in the former (35%) as compared to their absence in the latter (3%). Hybridization of metaphase preparations of 9 i(12p)‐negative tumors with a chromosome 12 painting probe and with a microdissected 12p painting probe revealed extra copies of chromosome 12 segments incorporated into marker chromosomes whose composition could not otherwise be resolved by banding analysis; all were shown to be derived from 12p. These data demonstrate that both i(12p)‐negative and ‐positive groups are characterized by an increased copy number of 12p, which is consistent with a lack of significant clinical or biological difference between them. An increased 12p copy number thus is a specific aberration of significance to the development of germ cell tumors. © 1993 Wiley‐Liss, Inc.
Translocation of BCR to chromosome 9: A new cytogenetic variant detected by FISH in two Ph‐negative, BCR‐positive patients with chronic myeloid leukemia
Authors: Hagemeijer Anne , Buijs Arjan , Smit Elizabeth , Janssen Bart , Creemers Geert‐Jan , Plas Dorien Van Der , Grosveld Gerard
Published: February 2007

Leukemic cells from two patients with Philadelphia‐negative chronic myeloid leukemia (CML) were investigated: I) Cytogenetics showed a normal 46.XY karyotype in both cases, 2) molecular studies revealed rearrangement of the M‐BCR region and formation of BCR‐ABL fusion mRNA with b2a2 (patient I) or b3a2 (patient 2) configuration, and 3) fluorescence in situ hybridization (FISH) demonstrated relocation of the 5′ BCR sequences from one chromosome 22 to one chromosome 9. The ABL probe hybridized to both chromosomes 9 at band q34, while two other probes which map centromeric and telomeric of BCR on 22q 11 hybridized solely with chromosome 22. For the first time, a BCR‐ABL rearrangement is shown to take place on 9q34 instead of in the usual location on 22q 11. A rearrangement in the latter site is found in all Ph‐positive CML and in almost all investigated CML with variant Ph or Ph‐negative, BCR‐positive cases. The few aberrant chromosomal localizations of BCR‐ABL recombinant genes found previously were apparently the result of complex and successive changes. Furthermore in patient 2, both chromosomes 9 showed positive FISH signals with both ABL and BCR probes. Restriction fragment length polymorphism (RFLP) analysis indicated that mitotic recombination had occurred on the long arm of chromosome 9 and that the rearranged chromosome 9 was of paternal origin. The leukemic cells of this patient showed a duplication of the BCR‐ABL gene, analogous to duplication of the Ph chromosome in classic CML. In addition they had lost the maternal alleles of the 9q34 chromosomal region. The lymphocytes of patient 2 carried the maternal chromosome 9 alleles and were Ph‐negative as evidenced by RFLP and FISH analyses, respectively. © 1993 Wiley‐Liss, Inc.
Identification of a novel protein with GDP dissociation inhibitor activity for the ras‐like proteins CDC42Hs and Rac 1
Authors: Adra Chaker N. , Ko Jon , Leonard David , Wirth Lori J. , Cerione Richard A. , Lim Bing
Published: February 2007

We have recently cloned the human cDNA for a gene, denoted D4, that encodes a protein 67% identical to the bovine rhoGDI protein, a GDP dissociation inhibitor (GDI) for the ras‐related rho‐subtype proteins. We now present data on the cloning and structural analysis of the murine D4 cDNA and confirm its preferential expression in hematopoietic tissues. The predicted murine and human D4 proteins are almost 90% identical, indicating that D4 and rhoGDI are different genes and that they are probably members of a related family of genes. Functional studies with the human D4 protein demonstrate that D4 has GDI activity against the CDC42Hs and rac I proteins, but binds to these proteins with a significantly weaker affinity than does the rho‐subtype GDI. These data suggest that D4, which will in subsequent communications be denoted as GDI.D4, might be a GDI for other known or as yet unidentified ras‐like GTP‐binding proteins. Alternatively, D4 could have other biochemical functions. During murine embryogenesis, D4 transcripts are detected in yolk‐sac cells, where the earliest hematopoietic precursors are found. When these precursors undergo proliferation and differentiation in vitro, a dramatic increase in D4 expression is seen. D4 probably has a significant function during the growth and development of hematopoietic precursors. © 1993 Wiley‐Liss, Inc.
Multiple genetic events involving rbi gene deletion and amplification of chromosome 21 in a case of acute lymphocytic leukemia
Authors: Liu Yie , Heyman Mats , Grandér Dan , Einhorn Stefan , Söderhäll Stefan , Bröndum‐Nielsen Karen
Published: February 2007

A patient with acute lymphocytic leukemia was found to have a hyperdiploid karyotype, characterized by hexasomy 21 and del(7)(p15). It was shown that the four extra copies of chromosome 21 were all derived from only one of the homologous chromosomes. Molecular analysis showed that the patient had a deletion of both alleles of the retinoblastoma (RBI) gene. These results suggest that multiple events, including loss of RBI gene function and amplification of a key gene(s) on chromosome 21, have contributed to the leukemic transformation. Genes Chrom Cancer 9:72‐75 (1994). © 1994 Wiley‐Liss, Inc.
Enhanced MYCN expression and lsochromosome 17q in pineoblastoma cell lines
Authors: Kees Ursula R. , Ford Jette , Ranford Pamela R. , Peroni Susanne E. , Biegel Jaclyn A. , Parmiter Annette H. , Hallam Lavinia A. , Willoughby Michael L. N. , Spagnolo Dominic
Published: February 2007

We have established two cell lines, PER‐452 and PER‐453, from an 8‐month‐old girl with an extensive pineoblastoma. Characterization of these lines revealed that the proto‐oncogenes MYC and MYCN were not amplified, but both cell lines showed MYCN expression comparable to a cell line with 200‐fold MYCN amplification. Both cell lines contained an i( 17q). These results support the concept that pineoblastomas belong to a larger group of primitive neuroectodermal tumors of the central nervous system. These two cell lines provide a unique opportunity to investigate the molecular genetic mechanisms underlying these neoplasms further. Genes Chrom Cancer 9:129‐135 (1994).© 1994 Wiley‐Liss, Inc.
There may be two tumor suppressor genes on chromosome arm Ip closely associated with biologically distinct subtypes of neuroblastoma
Authors: Takeda Osamu , Homma Chieko , Maseki Nobuo , Sakurai Masaharu , Kanda Naotoshi , Schwab Manfred , Nakamura Yusuke , Kaneko Yasuhiko
Published: February 2007

We studied loss of heterozygosity (LOH) on chromosome arm Ip in 108 neuroblastomas using 14 polymorphic DNA markers. One‐hundred and four tumors with one or more informative loci; 21 (20%) of the 104 tumors showed LOH on Ip, and were classified into three groups on the basis of interstitial or terminal allelic loss, and presence or absence of LOH on Ip. Seven of the 21 tumors showed an interstitial deletion which encompassed a small region in Ip36 (group A), and the other 14 showed a terminal deletion which encompassed the region from I pter to Ip32 (group B). Eighty‐three tumors without LOH on I p were classified as group C. The group A patients were mostly less than 12 months of age (6/7), were frequently found by a mass screening program for infants (5/7), had a tumor of non‐adrenal origin, and rarely progressed to stage IV (1/7). Most group B patients were 12 months or older (11/14), were found clinically (11/14), had tumors of adrenal origin, and progressed to stage IV (10/14). Analysis of biologic characteristics in group C tumors suggested that they may comprise group A and B tumors. While all group A tumors were in the triploid range (3n) (4/4), most group B tumors were diploid (2n) or tetraploid (4n) (7/10). MYCN amplification was found in 8 group B tumors, but in none of group A tumors. Event‐free survivals of groups A, B, and C patients at 3 years were 86, 49, and 74%, respectively (P = 0.0287). These findings suggest that there may be two tumor suppressor genes on Ip which are closely associated with two biologically distinct subtypes of neuroblastoma. Genes Chrom Cancer 10:30–39 (1994). © 1994 Wiley‐Liss, Inc.
Tumor progression in a giant cell type malignant fibrous histiocytoma of bone: Clinical, radiologic, histologic, and cytogenetic evidence
Authors: Molenaar Willemina M. , Berg Eva Van Den , Veth Rene P. H. , Dijkhuizen Trijnie , De Vries Elisabeth G. E.
Published: February 2007

A malignant fibrous histiocytoma (MFH) of bone arising in the fibula of a 21‐year‐old woman is described. Clinical, radiologic, and histologic findings demonstrated rapid tumor progression. Chromosomal analysis of the biopsy specimen showed great karyotypic heterogeneity, whereas the resection specimen four weeks later displayed a rather homogeneous karyotype. Both revealed a clonal t(14;22)(q11;p12). Several other clonal and non‐clonal chromosomal aberrations were observed. Some of these were previously described in giant cell tumor of bone (GCTB) and may correlate with aggressive behavior, e.g., aberrations involving 8p 11, 19q 13, and 20q 13. The change from karyotypic heterogeneity to relative homogeneity may be related to tumor progression. The chromosomal findings further suggest that the giant cell type of MFH of bone may be related to malignant GCTB. Genes Chrom Cancer 10:66–70 (1994). © 1994 Wiley‐Liss, Inc.
I;17 translocations and other chromosome 17 rearrangements in human primary neuroblastoma tumors and cell lines
Authors: Van Roy Nadine , Laureys Geneviève , Cheng Ngan Ching , Willem Pascale , Opedenakker Ghislain , Versteeg Rogier , Speleman Frank
Published: February 2007

We report on the finding of a t(1;17) in two primary neuroblastomas. Subsequent fluorescence in situ hybridization (FISH) analysis revealed the presence of 1; 17 transfocations in four out of nine neuroblastoma cell lines. The chromosome 1 short arm breakpoints were determined using region‐specific probes. FISH screening also demonstrated or confirmed the presence of 11;17 translocations in three cell lines and other chromosome 17 rearrangements in those cell lines that did not carry a t(1; 17) or t(11; 17). Our data extend previous cytogenetic findings and suggest that, in addition to the known involvement of chromosome I, one or more genes on chromosome 17 also play a role in neuroblastoma development. Genes Chromosom Cancer 10:103–114 (1994). © 1994 Wiley‐Liss, Inc.
Allelotype study of esophageal carcinoma
Authors: Aoki Takahisa , Mori Takahiro , Xiqun Du , Nisihira Tetsuro , Matsubara Toshiki , Nakamura Yusuke
Published: February 2007

To investigate genetic features of esophageal cancer, we have examined 93 squamous cell carcinomas of the esophagus for loss of heterozygosity (LOH), using 41 restriction fragment length polymorphism (RFLP) markers representing all autosomal chromosomes. Allelic losses at frequencies of at least 30% were observed at loci on chromosomal arms 3p (35%), 3q (30%), 5q (36%), 9p (57%), 9q (60%), 10p (33%), 13q (43%), 17p (62%), 17q (46%), 18q (38%), 19q (32%), and 21q (37%). These results suggest that several putative tumor suppressor genes, in addition to the cyclin D and TP53 genes that are sometimes mutated in esophageal carcinomas, may be associated with development and/or progression of esophageal cancer. By a comparison of LOH on each chromosomal arm with clinicopathological parameters, we have found a significant correlation between LOH on 19q and regional lymph node metastases. Interestingly, the frequency of LOH on 17q was significantly higher in tumors in female patients (12 of 14 cases) than in those in male patients (20 of 56 cases) (P = 0.0009 by Fisher's exact test). Furthermore, we examined for mutations of the APC gene on chromosome arm 5q. Screening of nearly one third of the APC coding region, including the MCR (mutation cluster region), revealed no alterations. Therefore, although allelic loss at the APC locus is frequent in squamous cell carcinomas of the esophagus, it is likely that a gene on 5q other than APC is involved in esophageal tumorigenesis. Genes Chromosom Cancer 10:177–182 (1994). © 1994 Wiley‐Liss, Inc.
Correlation of loss of heterozygosity at 11 p with tumour progression and survival in non‐small cell lung cancer
Authors: Fong Kwun M. , Zimmerman Paul V. , Smith Peter J.
Published: February 2007

Loss of heterozygosity (LOH) affecting loci at 11 p 13 and 11 p 15 occurs in childhood and adult carcinomas, including non‐small cell lund cancer (NSCLC). In NSCLC, the highest reported frequency of LOH was 72% at the 11 p 13 catalase (CAT) locus. As this locus is centromeric to the Wilms' tumour (WTI) locus, possible involvement of WTI in the pathogenesis of NSCLC was considered. We thus examined 101 cases of NSCLC for LOH at the WTI and five other polymorphic loci along 11 p. At 11 p 13, the frequencies of LOH were 20% (9/46) at the FSHB locus, 9% (5/53) at the WTI locus, and 15% (6/41) at the CAT locus. The shortest region of overlap (SRO) at 11p13 was mapped centromeric to, but excluding, the WTI locus. Only adenocarcinomas showed LOH in this region. At 11 p 15, LOH affected 23% (18/77) of informative cases, with the highest frequency of 36% at the insulin (INS) locus. The SRO at 11 p15 was mapped telomeric to the RRMI locus. A third region, at 11 p13–15 between WTI and RRMI, was also affected by LOH. LOH at 11p correlated significantly with advanced T stage and nodal involvement in NSCLC tumours. In the squamous cell carcinoma subtype, LOH along 11p also correlated with nodal involvement. Furthermore, squamous tumours with LOH involving 11p13 loci had significantly worse survival than those without LOH. These data suggest that tumor suppressor gene(s) on 11p affect the progression of NSCLC, particularly squamous cell carcinomas. Genes Chromosom Cancer 10:183–189 (1994). © 1994 Wiley‐Liss, Inc.
Isochromosomes in neoplasia
Authors: Mertens Fredrik , Johansson Bertil , Mitelman Felix
Published: February 2007

In order to ascertain the frequency and distribution of isochromosomes in neoplasia, we surveyed the cytogenetic data from 20,007 tumors with clonal chromosome aberrations reported in the literature. Tumor types for which at least 50 cases with acquired aberrations and 10 cases with isochromosomes had been reported were selected, yielding a total of 18, 160 neoplasms. Of these, 1,792 cases (9.9%) displayed a total of 2,014 isochromosomes. The 9 most common isochromosomes (detected in at least 50 cases) were, in decreasing order of frequency, i(17q), i(8q), i(lq), i(12p), i(6p), i(7q), i(9q), i(5p), and i(21q). The frequency of isochromosomes varied among the different tumor types, with the highest incidence in germ cell neoplasms (60%) and the lowest in chronic myeloproliferative disorders (2.3%). Also, the spectrum of isochromosomes differed among the neoplasms. The most common isochromosomes in the different tumor types were i(I Iq), i(I7q), and i(2Iq) in acute myeloid leukemia; i(9q), i(I7q), and i(22q) in chronic myeloid leukemia; i(I7q) in chronic myeloproliferative disorders; i(X)(qI3), i(I7q), and i(2Iq) in myelodysplastic syndromes; i(7q), i(9q), and i(I7q) in acute lymphoblastic leukemia; i(Iq), i(7q), i(8q), and i(I7q) in chronic lymphoproliferative disorders; i(Iq), i(6p), i(9p), i(I7q), and i(2Iq) in Hodgkin's disease; i(Iq), i(6p), and i(7q) in non‐Hodgkin's lymphoma; i(Iq), i(8q), and i(I7q) in adenocarcinoma; i(Iq), i(3q), i(5p), and i(8q) in squamous cell carcinoma; i(5p), i(8q), and i(IIq) in transitional cell carcinoma; i(Iq), i(7q), and i(I7q) in Wilms' tumor, i(Iq), i(I2p), and i(I7q) in germ cell neoplasms; i(Ip), i(Iq), i(6p), and i(I7q) in sarcoma; i(5p), i(6p), i(7p), and i(2Iq) in mesothelioma; i(lq), i(6p), and i(I7q) in malignant neurogenic neoplasms; i(Iq), i(6p), and i(I7q) in retinoblastoma; and i(Iq), i(6p), and i(8q) in malignant melanoma. Genes Chromosom Cancer 10:221–230 (1994). © 1994 Wiley‐Liss, Inc.
Detection of numerical and structural chromosome abnormalities in pediatric germ cell tumors by means of interphase cytogenetics
Authors: Stock Cornelia , Ambros Inge M. , Lion Thomas , Haas Oskar A. , Zoubek Andreas , Gadner Helmut , Ambros Peter F.
Published: February 2007

In contrast to the cytogenetically well characterized testicular germ cell tumors (GCT) in adults, reports on cytogenetic studies in pediatric GCT are scarce. The presence of an i(12p) and numerical abnormalities involving chromosome 12 are the most frequent cytogenetic changes in GCT of adults. We have performed in situ hybridization (ISH) studies on paraffin sections and on isolated nuclei of 13 pediatric GCT with particular emphasis on those chromosome abnormalities that are common in adult GCT. These include numerical and structural abnormalities of chromosomes 1 and 12 as well as numerical deviations of chromosomes 8, 10, X, and Y. The histological subsets of the tumors investigated included two dysgerminomas (DGE), one seminoma (SE), two embryonal carcinomas (EC), four mixed and two pure yolk sac tumors (YST), and one undifferentiated (IT) and one differentiated teratoma (TD). Similar to the GCT in adults, additional copies of chromosome 12 were the most frequently observed numerical abnormalities. In contrast to the findings in adult GCT, changes in the size of the pericentromeric hybridization signals of chromosome 12, suggesting the presence of i(12p) chromosomes, were found in only two cases. No chromosome abnormalities were found in the pure TD or in the TD cells of mixed tumors containing a YST component. In the YST portion, however, Ip deletions and/or numerical chromosome changes were present. Surprisingly, deletions of the short arm of chromosome I, del(I)(p36.3), were frequent in pediatric GCT and were the sole abnormality detected in two cases. The Ip36 deletions were present in all stage‐IV EC and YST investigated and were absent in the relatively benign TD and in one YST stage‐I. Therefore, Ip36 deletions may have value as a prognostic marker in pediatric GCT.
The two genes generating RET/PTC3 are localized in chromosomal band 10q11.2
Authors: Minoletti Fabiola , Butti Marta Giaele , Coronelli Silvia , Miozzo Monica , Sozzi Gabriella , Pilotti Silvana , Tunnacliffe Alan , Pierotti Marco A. , Bongarzone Italia
Published: February 2007

PCR analysis of DNA from a selected panel of human‐rodent somatic cell hybrids and fluorescent in situ hybridization (FISH) analysis allowed us to localize the human ELEI gene. This previously uncharacterized gene is fused with the tyrosine kinase (tk) domain of the RET proto‐oncogene to generate the oncogenic sequence RET/PTC3, thus providing a third example of RET oncogenic activation in papillary thyroid carcinomas. ELEI was localized to band 10q11.2, the subband where RET also maps, at a minimum distance of more than 500 kb from the proto‐oncogene. The fusion event corresponding to the rearrangement reciprocal to that leading to the formation of RET/PTC3 was also identified and characterized. The karyotype of two RET/PTC3 positive tumors did not show any evidence of chromosome 10 abnormalities. The data indicate that a cytogenetically undetectable paracentric inversion within 10q11.2 generates RET/PTC3.
Cloning and characterization of the t(X;II) breakpoint from a leukemic cell line identify a new member of the forkhead gene family
Authors: Parry Pauline , Wei Yalin , Evans Glen
Published: February 2007

Chromosome translocations involving 11q23 are associated with a number of different types of leukemia. These translocations fuse a gene encoding a putative transcription factor, HTRXI, to genes on other chromosomes. We report cloning and sequencing the t(X;II) breakpoint region from a cell line established from an infant with acute lymphocytic leukemia. The gene AFXI, on the X chromosome, is expressed in a variety of cell types. Sequence analysis indicates a high degree of homology between AFXI and the forkhead family of transcription factors. The high degree of identity within the forkhead region and the lack of homology outside that region suggest that AFXI represents a novel forkhead family member. It is predicted that a chimeric fusion protein with altered DNA binding activity will be the result of the translocation.
Analysis of glioma cell lines for amplification and overexpression of MDM2
Authors: He Ju , Reifenberger Guide , Liu Lu , Collins V. Peter , James C. David
Published: February 2007

Recently, amplification of the gene encoding a p53 binding protein, MDM2, was determined in 8% of the cases constituting a large series of glioblastomas. Here we have utilized Southern blot analysis to examine 30 cell lines established from such tumors, and our investigation has revealed large increases in MDM2 gene dosage in two cases, one of which showed coamplification of the CDK4 gene that resides in close proximity to MDM2 in chromosomal region 12q13–14. Northern analysis demonstrated overexpression of MDM2 mRNA in the two cell lines with gene amplification, and overexpression of MDM2 protein was evident in each of these by immunohistochemical and Western blot analysis. Analysis of TP53 cDNAs revealed normal TP53 sequences in the cell lines with MDM2 amplification; these results are consistent with those of previous studies suggesting that MDM2 amplification occurs only in tumors expressing wild‐type p53. In total, these data suggest that MDM2 amplification in glioblastoma cell lines occurs at a frequency (6.7%) comparable to that determined in primary tumors; occurs in cell lines expressing wild‐type p53; and can involve the coamplification of additional genes.
Localization of beckwith‐wiedemann and rhabdoid tumor chromosome rearrangements to a defined interval in chromosome band 11p15.5
Authors: Salt Sheila N. J. , Nowak Norma J. , Singh‐Kahlon Pal , Weksberg Rosanna , Squire Jeremy , Shows Thomas B. , Higgins Michael J.
Published: February 2007

Chromosome rearrangements have provided useful landmarks to identify disease loci and have served as starting points for positional cloning strategies for candidate genes. We have used fluorescence in situ hybridization (FISH) and pulsed‐field gel electrophoresis (PFGE) to map three Beckwith‐Wiedemann syndrome (BWS) breakpoints and a rhabdoid tumor breakpoint more precisely. These breakpoints mapped to the interval between D11S679 and the insulin‐like growth factor 2 (IGF2) gene on 11p15.5. A cosmid (c15‐2) was identified that mapped centromeric to the BWS t(11;16) and the rhabdoid tumor‐associated t(11;22), telomeric to the BWS t(11;22), and was found to span the BWS‐associated inv(11) breakpoint. Pulsed‐field gel analysis placed all four breakpoints into a 250‐675 kb interval distal to D11S679 and at least 270 kb centromeric to the IGF2 and H19 loci. These data locate all three BWS rearrangements and the rhabdoid tumor t(11;22) breakpoint in the same region of 11p 15.5, suggesting that they may be affecting the same locus or closely linked loci. Cosmid c15‐2 provides a well‐defined starting point in the search for candidate disease genes.