bluuebunny/crossref_metadata_2025 huggingface dataset:
Trisomy 7 and Sex Chromosome Loss Need Not Be Representative of Tumor Parenchyma Cells in Malignant Glioma
Authors: Lindström Elisabeth , Salford Leif G. , Heim Sverre , Mandahl Nils , Strömblad Susanne , Brun Arne , Mitelman Felix
Published: February 2007

We describe the cytogenetic findings in short‐term cultures from 40 malignant gliomas, all of which had at least one clone with a simple numerical chromosome aberration. More than one aberrant clone was found in 17 tumors. The most frequent changes were loss of a gonosome (sole aberration in 38 clones), trisomy 7 (sole aberration in four clones), and combinations thereof (the aberrations + 7 and — X or — Y were found together as the only changes in four clones). Clones with solitary trisomies for other autosomes—3, 5, 6, and 18—were seen in five tumors. Clones with structural rearrangements were found in nine tumors. The bands most commonly involved were I p36, 7p22, 9p22, 17p 13, and 19q 13. An extra copy of chromosome 7 was seen as part of a structurally abnormal clone in five tumors. In one case, trisomy 7 and even tetrasomy 7 were found in clones with simple numerical changes, but not in the clone with structural rearrangements. Likewise, the clonal loss of a gonosome was in six tumors, with structural abnormalities not present in the structurally aberrant clones; on the other hand, in two clones with structural aberrations a sex chromosome had been lost. The combined findings indicate that loss of a sex chromosome and trisomy 7 should not be seen as tumor‐specific aberrations in gliomas. Instead, both glioma parenchyma cells and nonneoplastic cells in brain tumors may have a propensity to acquire extra copies of chromosome 7 and to lose gonosomes.
Karyotype instability and altered differentiation of rat sarcoma cells after retroviral infection
Authors: Steffen Martin , Scherdin Ulrich , Hölzel Fritz , Vértes Isabella , Boecker Werner , Dietel Manfred
Published: February 2007

The karyotypic and phenotypic stability of cultured rat fibrosarcoma cells was challenged by infection with Moloney murine sarcoma virus (MoMuSV). After transformation, the spindle‐like morphology of the parental HH‐16 cl.2/1 cells had altered to a rounded phenotype, which was maintained in tumors produced by inoculating transformed cells into congenic animals. In contrast to the parental cells, transformed cells lacked cables of cytokeratins 14–16 and 19 and showed reduction of the mesenchymal marker protein vimentin. Additionally, the morphologically altered cell clones tf‐1 to tf‐3 had lost growth arrest in the presence of dexamethasone. The DNA of the transformed cells contained between four and six randomly integrated proviral copies. Karyotypic alterations were manifested by reduction of morphologically intact chromosomes in the MoMuSV‐transformed cells together with increase of structural aberrations. Three additional markers were identified in the virus‐transformed cell clones. Karyotypic instability induced by MoMuSV infection appeared closely related to reduction of the cellular differentiation status, although only cells of clone tf‐1 had increased metastatic potential.
Specific metaphase and interphase detection of the breakpoint region in 8q24 of burkitt lymphoma cells by triple‐color fluorescence in situ hybridization
Authors: Ried Thomas , Lengauer Christoph , Cremer Thomas , Wiegant Joop , Raap Anton K. , Ploeg Mels Van Der , Groitl Peter , Lipp Martin
Published: February 2007

Triple fluorescence in situ hybridization with a plasmid DNA library from sorted human chromosomes 8 in combination with bacteriophage clones flanking the breakpoint in 8q24 of the Burkitt lymphoma cell line Jl was used for the specific delineation of this breakpoint in individual tumor cells. With this approach, tumor‐specific breakpoints in translocation chromosomes can be detected at all stages of the cell cycle with high specificity.
Clonal aberrations of chromosomes x, y, 7 and 10 in normal kidney tissue of patients with renal cell tumors
Authors: Emanuel Angela , Szucs Sandor , Weier Heinz‐Ulrich G. , Kovacs Gyula
Published: February 2007

By means of G‐banding techniques, chromosome aberrations were studied in short‐term cultures of normal renal parenchymal cells from 45 patients with renal cell carcinoma. Clonal chromosomal aberrations were detected in 29 patients; loss of the Y chromosome as well as trisomy X, 5, 7, 9, 10, 12, and 18 was found. Chromosomes 7 and 10 were involved preferentially. Results of fluorescence in situ hybridization with chromosome 7‐ and 10‐specific DNA probes on non‐cultured normal kidney cells suggested that the aberrations developed in vivo.
Trisomy 2 as the sole chromosomal abnormality in a hepatoblastoma
Authors: Bardi Georgia , Johansson Bertil , Pandis Nikos , Heim Sverre , Mandahl Nils , Mitelman Felix , Békássy Albert , Hägerstrand Inga
Published: February 2007

Short‐term cultures of a fine‐needle aspirate from a hepatoblastoma were analyzed cytogenetically. Trisomy 2 was found as the sole abnormality, yielding the karyotype 47,XY, + 2/46,XY. Because trisomy for all or part of chromosome 2 has been described, although together with other aberrations, in seven of the 11 hepatoblastomas hitherto reported, the finding of +2 as the only anomaly in the present case strongly indicates that additional chromosome 2 material is of pathogenetic significance in this tumor type.
Interstitial loss of the same region of 5q in multiple adenomas and a carcinoma derived from an adenomatous polyposis coli (apc) patient
Authors: Miki Yoshio , Nishisho Isamu , Nakamura Yusuke , Miyoshi Yasuo , Utsunomiya Joji
Published: February 2007

Accumulation of genetic alterations in oncogenes and tumor suppressor genes causes the transformation of a normal cell into a malignant cell. Recently, Fearon and Vogelstein (Cell 61:759‐767, 1990) reported on a model for the genetic pathway in development of colorectal neoplasia. To investigate genetic alterations in colorectal carcinomas, we examined allelic losses on some chromosomes in adenomas and carcinomas derived from patients with adenomatous polyposis coli (APC). We found evidence for an interstitial deletion of 5q. Loss of heterozygosity (LOH) of 5q around the APC locus was observed in both adenoma and carcinoma in one case. The fact that the same region of chromosome 5 was lost in five adenomas and one carcinoma derived from the same patient suggests that a somatic interstitial deletion may be caused not by random mechanisms but by a specific mechanism.
The nm23 gene maps to human chromosome band 17q22 and shows a restriction fragment length polymorphism with bg/II
Authors: Varesco Lillana , Caligo Maria A. , Nardini Vincenzo , Bevilacqua Generoso , Casarino Lucia , Ferrar Giovanbattista , Simi Paolo , Rocchi Mariano , Black Donald M. , Solomon Ellen
Published: February 2007

The NM23‐HI gene is a putative tumor suppressor gene that may be important in the metastastic process. Recent genetic and immunological data indicate that the NM23‐HI gene encodes a protein with nucleoside diphosphate (NDP) kinase activity. The mapping of NM23‐HI by panels of rodent‐human somatic cell hybrids and in situ hybridization showed that the gene is located in human chromosome band 17q22. A two‐allele polymorphism with Bg/ll was demonstrated.
Cytogenetic abnormalities in an ossifying fibroma from a patient with bilateral retinoblastoma
Authors: Gollin Susanne M. , Storto Patrick D. , Malone Patrick S. , Washington Janice A. , Chidambaram Abirami , Barnes Leon , Janecka Ivo P.
Published: February 2007

Cytogenetic analysis of a cemento‐ossifying fibroma from a patient with nonfamilial bilateral multicentric retinoblastoma revealed three reciprocal translocations with the karyotype 46,XY,t(1;18)(q21;q21.3),t(3;10)(p13;q22),t(6;11)(p22;p15). Routine and high‐resolution cytogenetic analysis of peripheral blood leukocytes showed an apparently normal, 46,XY chromosome pattern with no deletion of chromosome 13. Molecular analysis demonstrated no gross differences in the retinoblastoma gene or the TP53 gene between constitutional and tumor DNA. This is the first cytogenetic analysis of a cemento‐ossifying fibroma and the first report of this tumor in a retinoblastoma patient. The data may be added to the small, but growing literature on cytogenetic aberrations in benign tumors and may lend insight into genes involved in cell proliferation and neoplastic transformation.
Linkage map of a region of human chromosome band 11q13 amplified in breast and squamous cell tumors
Authors: Brookes Sharon , Alistair Lammie G. , Dickson Clive , Peters Gordon , Schuuring Ed
Published: February 2007

DNA amplification involving markers on human chromosome band 11q13 is a consistent feature of several major cancers, notably adenocarcinoma of the breast and squamous cell carcinoma of the head, neck, lung, and esophagus. Since the presence of the amplification may be clinically significant, by defining a subset of patients at increased risk, it is important to establish which of the several genes on the amplified DNA provides the selective force. Here we describe a physical map of the centromeric end of the amplified DNA as it exists in a particular squamous carcinoma cell line (UMSCC2) and establish an unambiguous order for several known markers in the region, including pMSS1/D11S97, pHB159/D11S146, BCL1, PRAD1/D11S287, HSTFI/FGF4 and INT2/FGF3. Significantly, PRAD1 is within 120–150 kb of the BCL1 translocation breakpoint and the data identify a new CpG island (D11S814) between PRAD1 and HSTFI. The ordering of the HSTFI and INT2 genes and the clustering of CpG islands in the region have important implications in assessing whether the frequently observed amplifications at 11q13 are centered on one or more genes.
Malignant fibrous histiocytoma of the brain in a six‐year‐old girl
Authors: Biegel Jaclyn A. , Perilongo Giorgio , Rorke Lucy B. , Parmiter Annette H. , Emanuel Beverly S.
Published: February 2007

We have prepared karyotypes from a malignant fibrous histiocytoma (MFH) of the brain of a 6‐year‐old girl. Sporadic cases of MFH in the central nervous system have been reported. However, to our knowledge, this is the first central nervous system tumor to be subjected to cytogenetic analysis. The tumor demonstrated a complex karyotype, with a variety of numerical and structural abnormalities. Although no specific cytogenetic abnormality was observed, the karyotype of this case was similar to those reported for adult MFH of soft tissues.
Chromosome studies in plasma cell leukemia and multiple myeloma in transformation
Authors: Jonveaux Philippe , Berger Roland
Published: February 2007

Four patients with plasma cell leukemia (PCL) and two with multiple myeloma (MM) in transformation had complex numerical and structural chromosome abnormalities. From data published in the literature, the cytogenetic patterns of 46 cases of PCL or MM in the leukemic phase are compared with chromosomal abnormalities found in MM. Although the spectrum of chromosomal abnormalities is comparable in both diseases, the incidence of chromosome abnormalities is higher in PCL than in MM. Hypodiploidy with monosomies for chromosomes 13, 16, 17, and 18 is also more frequent in PCL than in MM. A mutation within the TP53 gene was detected in one of the three patients studied molecularly.
Expression of the ETS2 and transferrin receptor genes in Philadelphia‐positive chronic myeloid leukemia patients with a reciprocal t(3;21)
Authors: Lafage‐Pochitaloff Marina , Courcoul Marianne , Simonetti Jacqueline , Sainty Danielle , Dastugue Nicole , Tabilio Antonio , Hagemeijer Anne , Birg Françoise
Published: February 2007

The translocation t(3;21)(q26;q22) is a rare recurring clonal abnormality, either preceding or associated with blast crisis in Philadelphia chromosome‐positive chronic myeloid leukemia (CML) patients. We previously localized the chromosomal breakpoints at 3q26.2 and 21q22.2, using high resolution chromosomal analysis. Two genes of interest are localized near the breakpoints, the transferrin receptor gene and the ETS2 proto‐oncogene. Their chromosomal localizations, determined by in situ hybridization on normal metaphase cells, were 3q29 and 21q22.3, respectively. They underwent a reciprocal translocation in patients with t(3;21). Their structures were not altered by the translocation, and both were expressed to varying levels in t(3;21) patients. Southern blotting investigations showed that the structure of other single‐copy genes, including FIM3, localized near the breakpoints, were not affected by the translocation. An analysis of ETS2 expression performed on CML patients without t(3;21) showed the presence of the transcript in 100% of the blast crises, but only in 20% of the chronic‐phase patients. Thus ETS2 expression may either be linked to or play a role in CML progression.
Unicolor and bicolor in situ hybridization in the diagnosis of peripheral neuroepithelioma and related tumors
Authors: Desmaze C. , Zucman J. , Delattre O. , Thomas G. , Aurias A.
Published: February 2007

The chromosome 22 breakpoint of the t(11;22) translocation of peripheral neuroepithelioma has been located, by fluorescence in situ hybridization, in the proximity of the interface between 22q12.1 and 22q12.2. Use of single cosmids or pools of cosmids of the flanking regions enables the monitoring of the translocation in interphase and in metaphase chromosomes. This method can now be routinely applied for the diagnosis of this translocation in mixed round cell tumors.
Fusion and amplification of two originally non‐syntenic chromosomal regions in a mammary carcinoma cell line
Authors: Lafage Marina , Pedeutour Florence , Marchetto Sylvie , Simonetti Jacqueline , Prosperi Marie‐Thérèse , Gaudray Patrick , Birnbaum Daniel
Published: February 2007

The FLG/FGFRI gene, encoding a receptor for members of the FGF family, is located at 8p 11.2‐p12. It is amplified, overexpressed, and not grossly rearranged in the MDA‐MB‐134 breast carcinoma cell line, whereas other genes from the pericentromeric 8p region are not amplified. The FGF4/HSTFI gene, located at 11q13, is also amplified with a substantial portion of the 11q13 region, but is not overexpressed in MDA‐MB‐134 cells. In this cell line, amplified sequences constitute a large homogeneously staining region (HSR) which is part of a marker chromosome containing chromosome 8 and chromosome 11 sequences. Using probes for the FGF4/HSTFI and the FLG/FGFRI genes in fluorescence chromosomal in situ hybridization, we show that the HSR contains de novo fused and amplified 11q13 and 8p11‐p12 sequences associated in a complex structure containing approximately the same number of FGF4 and FGFRI genes. The significance of this genetic abnormality for MDA‐MB‐134 cells, and for breast carcinogenesis in general, is unknown, but may underlie a particular type of oncogene activation.
Loss of heterozygosity for 10q loci in human gliomas
Authors: Rasheed B. K. Ahmed , Fuller Gregory N. , Friedman Allan H. , Bigner Darell D. , Bigner Sandra H.
Published: February 2007

Cytogenetic and RFLP studies have shown that chromosome 10 is frequently lost in tumor cells from glioblastomas, suggesting that a suppressor gene important in tumorigenesis is present on this chromosome. Forty‐one tumors were examined for loss of heterozygosity at 23 loci on chromosome 10 to determine the smallest common deletion interval on this chromosome. Seven tumors did not lose heterozygosity for any of the markers. Twenty‐three tumors lost an allele for all the informative loci. In 11 tumors heterozygosity was maintained at some loci and lost at other loci, indicating partial deletion of chromosome 10. The common region of deletion in these 11 tumors was located in 10q24‐q26 between the markers pHUK‐8 and pMCT122.2.
Deletions in the short arm of chromosome 8 are present in up to 90% of human colorectal cancer cell lines
Authors: Van Der Bosch Kai , Becker Ilona , Savelyeva Larisa , Brüderlein Silke , Schlag Peter , Schwab Manfred
Published: February 2007

Cytogenetic analyses of human colon cancer cells have revealed non‐random deletions in chromosome arm 8p, among other chromosomal changes. By using 8p‐specific DNA probes we could identify allelic loss in 87% of colon cancer cell lines. Corresponding analyses in direct preparations of colon tumor tissues revealed a minimal value of 40% of allelic loss but were obstructed in many instances by contaminating normal tissue. These findings add to the number of non‐random genetic alterations occurring during colon carcinogenesis.
Wilms' tumor‐specific methylation pattern in 11p13 detected by PFGE
Authors: Royer‐Pokora Brigitte , Schneider Susanne
Published: February 2007

The analysis of 2,550 kb from 11 p 13 in Wilms' tumor (WT) material revealed two regions that differed significantly in their methylation between tumor and normal tissue. In WT a hypomethylated area defined by an Nrul and Mlul recognition site 100–150 kb centromeric of the WT gene WTI (site A) and hypermethylation defined by an Nrul and Sacll site 100 kb telomeric of the WTI gene were found (site B). The degree of methylation in region B varied between 20 and 100% in the different samples; the highest level was observed in tumors without preoperative chemotherapy. The CpG island 5′ of the WTI gene was partially methylated in 2/29 tumors analyzed. The methylation state of regions A and B could reflect the normal pattern present in a subset of embryonal kidney cells, from which WT develops.
Cytogenetic and molecular genetic characterization of papillary thyroid carcinomas
Authors: Sozzi Gabrielia , Bongarzone Italia , Miozzo Monica , Cariani Claudia T. , Mondellini Piera , Calderone Carla , Pilotti Silvana , Pierotti Marco A. , Porta Giuseppe Della
Published: February 2007

A combined cytogeneticand molecular analysis was performed on 11 cases of papillary thyroid carcinoma. A simple karyotypic abnormality was detected in five tumors, whereas six had no apparent chromosome change. In four of five rearranged cases the presence of a specific chromosomal abnormality involving chromosome 10 (cases 1 and 2) and chromosome I (cases 3 and 4) was associated with the rearrangement of two protooncogenes: RET and NTRKI(formerly trk), respectively, with different donor genes. Moreover, the chromosomal localization of the involved genes and the type of chromosomal change observed suggested that RET and NTRKI activation occurred by intrachromosomal rearrangements. The six cases with normal karyotype did not show RET or NTRKI activation. These findings suggest that a combined cytogenetic and molecular approach would be useful in understanding the pathogenesis of thyroid neoplasia.
Cloning and characterization of the Ewing's sarcoma and peripheral neuroepithelioma t(11;22) translocation breakpoints
Authors: Zucman Jessica , Delattre Olivier , Desmaze Chantal , Plougastel Béatrice , Joubert Isabelle , Melot Thomas , Peter Martine , De Jong Pieter , Rouleau Guy , Aurias Alain , Thomas Gilles
Published: February 2007

Ewing's sarcoma (ES) and peripheral neuroepithelioma (PN) are related tumors, possibly of neural crest origin, which are cytogenetically characterized by the specific translocation t(11;22)(q24;q 12). The cos5 locus, previously identified in the vicinity of the chromosome 22 breakpoint of this translocation, was shown by in situ hybridization on interphase nuclei to lie between VIIIF2 and LIF, two loci located on either side of the breakpoint and at a distance of less than 2,000 kb. The progressive expansion of this locus by chromosome walking led to the construction of a 300 kb contig, which finally crossed the breakpoint. The subsequent cloning of the two translocation junction fragments of a PN, followed by the molecular characterization of the translocation breakpoints of 20 ES and PN, showed that most chromosome 22 breakpoints are clustered within a small, 2 kb region. In contrast, the chromosome 11 breakpoints are scattered over a region of at least 40 kb. The translocation leads to the synthesis of a chimeric transcript that links sequences from chromosomes 22 and 11. Finally, no evidence was found of any specific difference in the position of ES and PN translocation breakpoints.
Chromosome I alterations in breast cancer: Allelic loss on Ip and Iq Is related to lymphogenic metastases and poor prognosis
Authors: Borg Åke , Zhang Qiu‐Xia , Olsson Håkan , Wenngren Eva
Published: February 2007

The development of human breast cancer is characterized by a variety of genetic alterations, and cytogenetic analyses have documented the consistent involvement of both arms of chromosome I. In the present study, molecular markers detecting restriction fragment length polymorphisms were used in pairwise screening of normal and tumor DNA to determine the frequency of allelic imbalance in breast tumors. Loss of heterozygosity (LOH) in the polymorphic epithelial mucin (PEM or MUCI) gene at 1q21 was found in 16% of 89 informative (constitutionally heterozygous) cases, whereas gain in intensity of one allelic band was more frequent (37%), a total of 47% of cases manifesting either allelic loss or gain. Three additional tumors manifested a structural alteration. Allelic loss or gain in the PEM gene was not associated with other prognostic factors, e.g., tumor size, lymph node status, steroid receptors, DNA ploidy, S phase fraction, protooncogene amplification, histological type, or patient age. However, LOH in the PEM gene was significantly correlated with early disease recurrence (P = 0.006). LOH on 1p was found in 27% of 117 informative cases, using probes for either DIS57 or DIZ2 located at 1p33‐p35 and 1p36, respectively. Somatic allelic imbalance on 1p and 1q seemed to be independent events and not the effect of loss of a whole chromosome 1. LOH on 1 p was significantly correlated to the presence of lymph node metastasis, to larger tumor size, and to DNA nondiploidy, but no correlation was found to disease outcome at this limited duration of follow‐up (median 29 months). ©1992 Wiley‐Liss, Inc.
Loss of heterozygosity mapping in Wilms tumor indicates the involvement of three distinct regions and a limited role for nondisjunction or mitotic recombination
Authors: Coppes Max J. , Bonetta Laura , Huang Annie , Hoban Paul , Chilton‐MacNeill Susan , Campbell Chris E. , Weksberg Rosanna , Yeger Herman , Reeve Antony E. , Williams Bryan R. G.
Published: February 2007

Loss of heterozygosity (LOH) for polymorphic markers is a frequently occurring event in some tumors, reflecting the role of allele loss in the development of these tumors. We have determined LOH in 38 cases of Wilms tumor for the 2 known loci on chromosome arm 11p and for a newly detected locus on chromosome arm 16q. Only 7 of the 38 tumors studied showed reduction to homozygosity of 11p13 markers. In 4 of these tumors, reduced expression of WTI and WITI, genes located at 11p13 and implicated in Wilms tumorigenesis, was noted. However, this was also found in 2 of 7 tumors showing LOH exclusively of 11p15 markers and in 15 of the remaining 24 tumors in which there was no LOH for 11p markers. This suggests that events not involving mitotic recombination or chromosome nondisjunction are the most common mechanisms for mutations at the 11p Wilms tumor locus. We also noted that mitotic recombination involving 11p15 loci occurred in addition to reduced expression of the 11p 13 locus genes in 2 tumors, suggesting a possible interaction between these 2 loci. In addition, LOH for 16q markers was observed in 6 tumors. In one case this was coincident with reduction of WTI and WITI gene expression, and in 3 other cases it occurred in addition to 11p LOH. This indicates that an additional locus on 16q is likely to be involved in Wilms tumorigenesis. © 1992 Wiley‐Liss, Inc.
Subiocalization of the chromosome 5 breakpoint of the 3;5 translocation in myelodysplastic syndromes and acute myeloid leukemia
Authors: Morris Stephan W. , Foust John T. , Valentine Marcus B. , Roberts W. Mark , Shapiro David N. , Look A. Thomas
Published: February 2007

A t(3;5)(q25.1;q34) reciprocal translocation identifies a subset of cases of myelodysplastic syndrome or acute myeloid leukemia (AML) that are characterized by increased numbers of megakaryocytes and severe trilineage dysplasia. As a first step in characterizing the t(3;5) breakpoints, we asked whether the translocation involves the CSFIR/PDGFRR locus at 5q33‐q35. Pulsed‐field gel electrophoretic analysis of a region extending 580 kb 5′ to the PDGFRB gene and 120 kb 3′ to the CSFIR gene did not reveal aberrant restriction fragments in leukemic cell DNA, confirming that the breakpoint does not occur in the vicinity of these genes. To sublocalize the breakpoint, we performed Southern blot hybridizations using DNA from human × hamster somatic cell hybrids containing the normal 3, the normal 5, the derivative 3, or the derivative 5 human chromosome. Using a series of polymorphic DNA probes from the long arm of chromosome 5, which have been linked by genetic recombination, we bracketed the breakpoint to within a region that spans ∼ 13 centimorgans (sex average) and is flanked by the q34‐qter markers cKK5.19 and L1200 (D5S62). This analysis places the chromosome 5 breakpoint of the t(3;5) considerably telomeric to the CSFIR/PDGFRB locus, confirming our studies with pulsed‐field electrophoresis. Future efforts to identify the genes affected by the t(3;5) should focus on the 5q segment described in this study. © Wiley‐Liss, Inc.
Human RAG2, like RAGI, is on chromosome II band p13 and therefore not linked to ataxia telangiectasia complementation groups
Authors: Sherrington P. D. , Forster A. , Seawright A. , Van Heyningen V. , Rabbitts T. H.
Published: February 2007

Ataxia telangiectasia (A‐T) is an inherited, recessive, cancer‐prone disease with associated immunodeficiency and chromosome abnormalities involving TCR loci. The latter phenomena implicate errors of the enzyme(s) responsible for assembly of antigen receptor genes (recombinase) in disease pathogenesis. Here we report the location of a human recombination activating gene (RAG2), in addition to RAGI, on chromosome 11, band p13, thereby formally demonstrating linkage of these genes in humans and showing that they are not linked to the known locus responsible for the A‐T syndrome. © 1992 Wiley‐Liss, Inc.
Cytogenetic abnormalities in non‐small cell lung carcinoma: Similarity of findings in conventional and feeder cell layer cultures
Authors: Siegfried Jill M. , Hunt Jay D. , Zhou Jian‐Yuan , Keller Steven M. , Testa Joseph R.
Published: February 2007

Primary tumors from 39 patients with non‐small cell lung carcinoma (NSCLC) were examined for cytogenetic abnormalities by conventional short‐term harvest (1–39 days) of primary cultures of minced solid‐tumor tissues and by harvest of monolayer cultures of tumor tissue (6 days to 5 months) on murine fibroblast feeder layers. A successful karyotype was obtained with both methods in nine of 39 cases. Among the remaining 30 cases, a successful karyotype was obtained in eight cases by the conventional method only and in three cases by the feeder cell method only. The success rates were 44% for the conventional method, and 31% for the feeder cell method, and the combined success rate was 51% for one or the other method. The feeder culture method, in which harvests were usually performed at later times than with the conventional method, generally produced metaphases with superior banding, which allowed clearer definition of cytogenetic abnormalities. In addition, cell lines were established in eight of these cases by the feeder cell method. Karyotypes from the longer‐term harvests typically were very similar to those from short‐term conventional cultures. Minor numerical differences and/or a few additional structural abnormalities were noted in seven of the nine cases analyzed by both methods. Overall, however, even in karyotypes from 5‐month cultures, the prominent recurrent changes and modal chromosome numbers observed in short‐term cultures were still present. The results indicate that long‐term culture with fibroblast feeder cells is a valid means of obtaining cells from solid lung tumors for cytogenetic and molecular analysis. Cell lines established by this method will be useful in future molecular studies, for example, for mapping of chromosome breakpoints and sites of chromosome loss, for in situ hybridization, and for studies of the expression of critical candidate genes implicated by cytogenetic findings. In addition, by combination of conventional and feeder cell harvests, both the number of primary tumors successfully examined karyotypically and the quality of the analyses are improved.© 1993 Wiley‐Liss, Inc.
ZFY gene expression and retention in human prostate adenocarcinoma
Authors: Tricoli James V. , Bracken R. Bruce
Published: February 2007

The terminal portion of the short arm of the human Y (Yp) chromosome encodes a zinc‐finger DNA binding protein (ZFY). A highly homologous gene, ZFX, is encoded on Xp. The potential of the zinc finger motif for regulating the expression of other genes suggests a role for this protein in the development of malignancy. Prostate adenocarcinoma is a malignancy of malespecific tissue, the incidence of which increases beyond the fifth decade of life. We have analyzed samples of human prostate adenocarcinoma for the expression of ZFY and ZFX transcripts. We found expression of ZFY transcripts in 3 of 31 prostate adenocarcinomas by using Northern analysis. No ZFY or ZFX transcripts were detected in normal hypertrophic prostate tissue on Northern analysis. In one prostate adenocarcinoma, high levels of the 5.1 kb ZFY and the 8.0 and 6.3 kb ZFX transcripts were present. In addition, this high‐grade tumor contained a novel 4.3 kb transcript. When we used reverse transcriptase PCR (RT‐PCR) to analyze these same samples, the number of tumors expressing ZFY and/or ZFX transcripts increased to 20 of 31. Transcripts for these genes were also present in the DU‐145 and LNCaP human prostate adenocarcinoma cell lines. In 2 of the 6 benine prostatic hypertrophy (BPH) tissues analyzed by RT‐PCR, barely detectable products of ZFY were observed, and none contained ZFX products. Southern analysis revealed that the portion of the Y chromosome which contains the ZFY gene was not lost from the majority of the tumor cells in any of the prostate malignancies examined. Our results demonstrate that ZFY and ZFX genes can become transcriptionally active in human tumors. We suggest that one possible outcome of this expression is the potential deregulation of other important growth control genes which could contribute to prostate malignancy. © 1993 Wiley‐Liss, Inc.
Detection of somatic changes in human renal cell carcinomas with oligonucleotide probes specific for simple repeat motifs
Authors: Bock Susanne , Epplen Jörg T. , Noll‐Puchta Heidi , Rotter Michael , Höfler Heinz , Block Thomas , Hartung Rudolph , Jakse Gerhard , Wilmanns Wolfgang , Petrides Petro E.
Published: February 2007

The purpose of our study was to detect somatic changes in renal cell carcinoma by multilocus fingerprinting. DNA fingerprints were generated from the DNA of normal and malignant renal tissue samples of 29 patients with nonhereditary kidney carcinoma by using oligonucleotide probes specific for simple repeat motifs such as (GTG)5, (CA)8, (GACA)4, or (TTAGGG)3. Each probe resdered a typical fingerprint pattern, because it is specific with respect to the target regions recognized in the genome. The restriction enzymes used were Hinfl and HaeIII. Changed banding patterns were detected by using (GTG)5 in 20% of the tumors, in 20% for (CA)8 after Hinfl digestion, and in 10% after HaeIII digestion. Even more informative probes were (GACA)4, showing 70% changes after HaeIII digestion, and (TTAGGG)3, with 80% changes after digestion with either enzyme. Since the simple repeat motifs recognized by (GACA)4 are localized on the short arms of the acrocentric chromosomes (13, 14, 15, 21, and 22), it is possible that sequences important for renal carcinogenesis are present in these regions. The observation of changes in regions to which (TTAGGG)3 hybridizes points to an involvement of DNA elements in telomeric sequence related regions in human kidney tumor formation. © 1993 Wiley‐Liss, Inc.
A submicroscopic interstitial deletion of chromosome 14 frequently occurs adjacent to the t(14;18) translocation breakpoint in human follicular lymphoma
Authors: Zelenetz Andrew D. , Cleary Michael L. , Levy Ronald
Published: February 2007

The t(14;18) chromosomal translocation characteristic of follicular lymphoma (FL) juxtaposes the immunoglobulin heavy chain locus (IGH) and the BCL2 proto‐oncogene. The translocation can be readily detected as a non‐germline Notl fragment resolved by pulsed‐field gel electrophoresis. A benefit of this approach is that it enables examination of the structure of a large region (±300 kb) surrounding the chromosomal breakpoint. In 40/46 cases the observed translocated Notl fragment was smaller than the 680–690 kb expected from published restriction maps of the involved loci suggesting a deletion in the region of the breakpoint. Analysis of the der(14) allele by molecular hybridization demonstrated that in 35/46 cases the μ. constant region (Cμ) was deleted. Further molecular dissection of the IGH locus demonstrated that this resulted from an interstitial deletion of the der(14) chromosome within the region defined by the μ switch region (Sμ) on the 5′ side and the ϵ constant region (Cϵ) on the 3′ end. Thus, the deletion resembled a class switch (CS) recombination event. Surprisingly, the CS deletion was as common in FL which was sIGM positive (24/33, 72.7%) as in cases where the productive allele had already undergone CS deletion (11/13, 84.6%) suggesting that the observed non‐physiologic CS deletion resulted from a cis effect of the chromosomal translocation. Similar interstitial deletions of the non‐productive IGH allele were not seen in B cell lymphocytic lymphomas which do not have the t(14;18) translocation. Mapping of the 3′ extent of the deletion by an isotype PCR assay demonstrated frequent involvement (11/12 cases) of the γ1 constant region (Cγ1). Analysis of cases in which the deletion was not evident by Southern blotting but detectable by PCR suggested that the CS deletion had occurred in a small subpopulation of FL cells subsequent to the t(14;18) translocation. The biological role of frequent interstitial deletions of the der (14) chromosome in t(14;18)‐carrying lymphomas remains to be elucidated. © 1993 Wiley‐Liss, Inc.
Interstitial deletion of the short arm of chromosome 3 as a primary chromosome abnormality in carcinomas of the breast
Authors: Pandis Nikos , Jin Yuesheng , Limon Janusz , Bardi Georgia , Idvall Ingrid , Mandahl Nils , Mitelman Felix , Heim Sverre
Published: February 2007

Interstitial deletions of the short arm of chromosome 3 were found in short‐term cultures of five breast carcinomas (of 41 breast cancers with clonal aberrations analyzed by us during the same period). They were the only clonal structural change in three tumors; in the remaining two, the clone with 3p– coexisted with seemingly unrelated clones that had other structural and numerical aberrations. The deletions were identical, del(3)(p12p14), in four cases. The fifth tumor seemed to have a smaller deletion, interpreted as del(3)(p13p14). Our findings constitute karyotypic evidence that 3p deletions are relatively common in breast carcinomas and concur with the molecular genetic detection of loss of heterozygosity in this chromosome arm. The fact that the deletions were found as solitary changes indicates that loss of genetic information from 3p loci is an early, possibly primary, event in tumorigenesis. © 1993 Wiley‐Liss, Inc.
Chromosome anomalies in mammary carcinoma from transgenic WAPRAS mice: Comparison with human data
Authors: Roy Henri Le , Ricoul Michelle , Ogata Hiromitsu , Apiou Françoise , Dutrillaux Bernard
Published: February 2007

Transgenic WAPRAS mice, obtained by infection of the construct WAP promoter murine gene and the HRAS human protooncogene, develop mammary adenocarcinoma within 1–3 months after pregnancy. A cytogenetic analysis was performed on 17 tumors from 10 mice. Almost all detected anomalies were chromosome gains. The resulting trisomies affected recurrently chromosomes 1, 15, 19, 17, 7, and 12, in decreasing order of involvement. Although in situ hybridization showed that the transgene was integrated in chromosome 1, the duplication of this chromosome did not depend on the presence or absence of the transgene. Comparison with human data indicates that the 3 most frequently duplicated chromosomes in WAPRAS mice correspond to the human chromosome segments most frequently duplicated or amplified in breast cancer, i.e., 1q, 8q, and 11q13. None of the chromosome segments often deleted in human tumors were found to be duplicated in the mouse tumors. © 1993 Wiley‐Liss, Inc.
Uniparental origin of i(12p) in human germ cell tumors
Authors: Sinke Richard J. , Suijkerbuijk Ron F. , Jong Bauke De , Oosterhuis J. Wolter , Van Kessel Ad Geurts
Published: February 2007

We present molecular data to demonstrate that the isochromosome 12p, specific for human germ cell tumors (GCTs), is of uniparental origin. Eight GCT‐derived cell lines, containing one or more copies of i(12p) and/or other 12p anomalies, were analyzed with different 12p‐derived polymorphic markers. The results from Ma‐90, a near‐diploid cell line with only one i(12p) in addition to two copies of a normal chromosome 12, clearly show an allelic 12p ratio of approximately 3:1, indicating that both 12p arms are of identical parental origin. These results were further substantiated by data obtained from the other i(12p)‐positive GCT‐derived cell lines. Therefore, we conclude that the i(12p) in GCTs constitutes a genuine isochromosome with genetically identical arms. The isochromosome most likely originates from a misdivision of the centromere rather than from a translocation or a non‐sister chromatid exchange as proposed by others. We also found that supernumerary 12p copies, as observed in i(12p)‐negative GCTs, are of uniparental origin. These observations seem to point to an important role for certain 12p‐derived sequences in the development of human GCTs. © 1993 Wiley‐Liss, Inc.
Clonal chromosome aberrations in cell cultures of synovial tissue from patients with rheumatoid arthritis
Authors: Ermis Ayhan , Hopf Thomas , Hanselmann Rainer , Remberger Klaus , Welter Cornelius , Dooley Steven , Zang Klaus D. , Henn Wolfram
Published: February 2007

Cytogenetic analysis of primary cell cultures and/or passages 1–3 of synovial tissue from seven patients with rheumatoid arthritis was performed. As the only recurrent chromosome aberration, trisomy 7 was found in six of seven cultures. In four cultures, trisomy 7 occurred as a clonal change in up to 20% of the analyzed cells, with an increase of the proportion of cells with +7 with the duration of the in vitro culture. Apart from this recurrent change, a variety of partly clonal, partly nonclonal numerical and structural chromosome aberrations were observed in all cases. These findings support the view that clonal chromosome aberrations may play a role in the pathogenesis of invasive growth of the synovial tissue in rheumatoid arthritis although the localized synovial hyperproliferation is not a true neoplastic process. © 1993 Wiley‐Liss, Inc.
Ring chromosome 6 as the only change in a thymoma
Authors: Cin Paola Dal , De Wolf‐Peeters Chris , Aly Magdy S. , Deneffe Georges , Van Mieghem Walter , Van Den Berghe Herman
Published: February 2007

Cytogenetic analysis of a thymoma showed the presence of a ring chromosome 6 as the sole chromosome abnormality. © 1993 Wiley‐Liss, Inc.
A second case of trisomy 8 in philadelphia chromosome (Ph)‐negative cells during the course of Ph‐positive chronic myelocytic leukemia
Authors: Bilhou‐Nabera C. , Marit G. , Devianne I. , Viard F. , Salzes S. , Montastruc M. , Renoux M. , Broustet A. , Reiffers J. , Bernard Ph.
Published: February 2007

A Ph‐positive CML patient who had received a peripheral blood stem cell autograft in chronic phase demonstrated a transient regression of the Ph‐positive clone with the concurrent appearance of another clone with trisomy 8. This latter clone disappeared when the patient received α‐interferon. © 1993 Wiley‐Liss, Inc.
A t(11;12) 11q23 leukemic breakpoint that disrupts the MLL Gene
Authors: Sait Sheila N. Jani , Raimondi Susana C. , Look A. Thomas , Gill Heidi , Thirman Michael , Diaz Manuel O. , Shows Thomas B.
Published: February 2007

Translocations involving 11q23 have been shown to be a consistent finding in human hematopoietic malignancies and in some constitutional abnormalities. The identification of a gene, MLL (myeloid/lymphoid or mixed‐lineage leukemia), that spans the breakpoints in four different recurrent 11q23 translocations was recently reported. We describe a rare (11;12)(q23;p13) translocation, observed in leukemic cells from a patient with acute lymphoblastic leukemia, which also disrupts this gene. © 1993 Wiley‐Liss, Inc.
Deletion of chromosome 11 and of 14q sequences in neuroblastoma
Authors: Srivatsan Eri S. , Ying Kuang Lin , Seeger Robert C.
Published: February 2007

Restriction fragment length polymorphism (RFLP) analysis carried out on 45 primary neuroblastomas showed deletion of chromosome 11 sequences in 12 of 37 (32%) informative cases. Both 11p and 11q probes were informative in seven tumors; loss of all of chromosome 11, of only 11p sequences, and of only 11q sequences was observed in 4, 1, and 2 tumors, respectively. A cytogenetic abnormality involving translocation of chromosome arm 11q to chromosome arm 1p was observed in a primary tumor. Deletion of 14q was observed in 6 of 27 (22%) informative cases. Deletion of chromosome 11 but not 14q may correlate with regional and metastatic disease. These results suggest a possible role for sequences localized to chromosome 11 and to 14q in the development and/or progression of neuroblastoma. © 1993 Wiley‐Liss, Inc.
Molecular analysis of a t(11;14)(q23;q11) from a patient with null‐cell acute lymphoblastic leukemia
Authors: Burnett Robert C. , Espinosa Rafael , Shows Thomas B. , Eddy Roger L. , Lebeau Michelle M. , Rowley Janet D. , Diaz Manuel O.
Published: February 2007

/1p;&‐3qChromosome 11, band q23, is the frequent site of recurring cytogenetic rearrangements in human leukemia. We have cloned and sequenced the breakpoint junctions from a patient who had null‐cell acute lymphoblastic leukemia (ALL) with a t(11;14)(q23;q11). The chromosome 14 breakpoints occurred within the TCRD locus, close to two diversity segments. The chromosome 11 breakpoint occurred between two head‐to‐head heptamer sequences, and junctional diversity was evident at both derivative junctions, suggesting involvement of the V(D)J recombinase. The TCRA/D locus on the normal chromosome 14 had undergone a Vδ2‐Dδ3‐ΨJα joining. Two phage clones with this VDJ rearrangement were isolated; one of these contained an intra‐Jα region deletion. Two clones with the derivative 11 junction were isolated; one of these had a similar, but not identical, deletion. A heptamer‐nonamer recognition sequence (located ∼70 kb 5′ to Cα), not associated with a TCR gene coding segment, was found in the immediate vicinity of both 5′ breakpoints. We have designated this sequence 5′del for 5′ deleting element. An intra‐Jα region deletion involving this heptamer‐nonamer was previously identified in the leukemia cells recovered from a patient who had T‐cell ALL. Fifty kilobases of DNA on 11q23 surrounding the breakpoint were cloned and analyzed. No CpG islands or conserved sequences were identified within this region. Fluorescence in situ hybridization analysis showed that this 11q23 breakpoint mapped distal to the MLL gene associated with the recurring breakpoints in the 4;11, 9;11, and 11;19 translocations, distal to the RCK gene associated with an 11;14 translocation, and proximal to the ETSI gene, which is located at 11q24. © 1993 Wiley‐Liss, Inc.
Telomeric associations in a patient with B‐cell prolymphocytic leukaemia
Authors: Howell Rodney T. , Kitchen Clare , Standen Graham R.
Published: February 2007

Telomeric associations were determined in bone marrow preparations from a patient with B‐cell prolymphocytic leukaemia and a clonal isochromosome of the long arm of chromosome 17. Thirteen associations involved 16 chromosome arms, with preferential involvement of the short arm of chromosome 19 and the long arm of 17. © 1993 Wiley‐Liss, Inc.
Translocation (11;22)(p13;q12): Primary change in intra‐abdominal desmoplastic small round cell tumor
Authors: Biegel Jaclyn A. , Conard Katrina , Brooks John J.
Published: February 2007

We present the cytogenetic findings in a case of a newly described tumor of childhood, intra‐abdominal desmoplastic small round cell tumor (IADSRCT). The karyotype demonstrated a single chromosomal translocation, (11;22)(p13;q12). © 1993 Wiley‐Liss, Inc.
Hypermutation of the MYC gene in diffuse large cell lymphomas with translocations involving band 8q24
Authors: Bradley John F. , Rothberg Paul G. , Ladanyl Marc , Chaganti R. S. K.
Published: February 2007

The sequence of the exon 1/intron 1 boundary region of the MYC gene was determined in two diffuse large cell lymphomas (DLCL), one with t(8;14) (q24;q32) and the other with t(8;22) (q24;q11). Both tumors had multiple mutations in this region. Also, both tumors had mutations in the protein binding site in intron I, which is a frequent target for mutational inactivation in endemic Burkitt's lymphoma (eBL). The translocations at 8q24, and multiple mutations in the exon 1/intron 1 boundary region, are reminiscent of similar findings in eBL. The same underlying oncogenic event that occurs in most eBLs is thus found in some DLCLs. © 1993 Wiley‐Liss, Inc.
Clonal t(8;14)(p11;q31) in a case of reactive lymphoproliferation
Authors: Zhang Yanming , Schlegelberger Brigitte , Plendl Hansjörg , Sonnen Ruth , Kuse Rolf , Feller Alfred C. , Grote Werner
Published: February 2007

A clone with an unbalanced translocation t(8;14)(p11;q31), resulting in deletion of the distal part of the long arm of chromosome 14, 14q31 → 14qter, was detected in a case of Piringer's lymphadenitis. Histopathologically no atypical cells or other signs of malignant lymphoma were found. Southern blot analyses showed no rearrangement of the immunoglobulin heavy chain gene (IGH) or the T‐cell receptor γ chain (TCRG) gene. The case exemplifies that the detection of a chromosomally aberrant clone does not necessarily prove that a lymphoproliferative process is malignant. © 1993 Wiley‐Liss, Inc.
Clonal chromosome abnormalities in human breast carcinomas I. Twenty‐eight cases with primary disease
Authors: Thompson Floyd , Emerson Julia , Dalton William , Yang Jin‐Ming , McGee Daniel , Villar Hugo , Knox Sally , Massey Kathy , Weinstein Ronald , Bhattacharyya Achyut , Trent Jeffrey
Published: February 2007

Cytogenetic analysis was performed on a selected series of short‐term cultures of primary breast carcinomas from 28 patients. All patients had histopathologically confirmed malignancies, with the majority (25/28 cases) demonstrating infiltrating ductal carcinoma. All 28 cases evidenced clonal chromosome abnormalities, with 10/28 displaying only numeric aberrations, whereas 18/28 displayed clonal structural alterations. In near‐diploid tumors the most common numeric changes were — 17 and — 19. However, trisomy 7 was the only numeric change in two near‐diploid tumors. Structural chromosome alterations were primarily isochromosomes, apparent terminal deletions, and unbalanced non‐reciprocal translocations. Chromosomes 1 (10/18–56%) and 6 (8/18–44%) were most frequently altered in this series. Breakpoints of clonal structural abnormalities were shown to cluster to several chromosome segments, including 1p22‐q11, 3p11, 6p11–13, 7p11‐q11, 8p11‐q11, and 19q13. Analysis of the gain or loss of specific chromosome segments revealed that the most consistent tendency was over‐representation of 1q, 3q, and 6p. © 1993 Wiley‐Liss, Inc.