bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytogenetic and molecular analysis of 6q deletions in burkitt's lymphoma cell lines
Authors: Parsa Nasser Z. , Mukherjee Asit B. , Chaganti R. S. K. , Gaidano Gianluca , Hauptschein Robert S. , Dalla‐Favera Riccardo , Lenoir Gilbert
Published: February 2007

Although abnormalities of chromosome 6 have frequently been observed in Burkitt's lymphoma (BL), they have 50 far not been defined by modern cytogenetic and molecular methods. By a combination of high‐resolution chromosome banding, fluorescence in situ hybridization (FISH), and loss of heterozygosity (LOH) analysis, we have examined the nature of aberrations affecting chromosome 6 in 7 previously established BL cell lines. All cell lines exhibited the characteristic translocations associated with BL; 5 had t(814)(q24;q32) and 2 had t(8;22)(q24;q11). Three cell lines had deletions of 6q; 3 others had rearrangements affecting 6q, whereas one cell line had apparently normal chromosomes 6. FISH analysis of the three deletions established that they were interstitial. LOH analysis with probes mapped to the 6q26‐27 region confirmed the sub‐telomeric interstitial deletion in cell line BL‐108, which had a del(6)(q23q27). All informative loci mapped to 6q26‐27 (5/7) were deleted in BL‐74, which had no apparent cytogenetic abnormality in chromosome 6, thus documenting a sub‐microscopic deletion. These data define the cytogenetic and molecular limits of 6q deletions in BL and are consistent with our previous demonstration of LOH analysis of the site of a candidate tumor suppressor gene in the 6q25‐27 region. Genes Chrom Cancer 9:13‐18 (1994). ©1994 Wiley‐Liss, Inc.
Mapping of the 8q23 translocation breakpoint of t(8;13) observed in a patient with multiple exostoses
Authors: Yoshiura Koh‐Ichiro , Inazawa Johji , Koyama Kumiko , Nakamura Yusuke , Niikawa Norio
Published: February 2007

A detailed cytogenetic map was constructed around the chromosomal breakpoint of t(8;13) observed in a patient with multiple exostoses. The order of seven loci defined by cosmid clones mapped to 8q23 was determined by means of two‐color fluorescence in situ hybridization (FISH) on elongated prophase chromosomes, and localizations of these markers relative to the breakpoint were examined. The results indicated that loci defined by cC18‐553 and cC18‐1512 flank the breakpoint. By pulsed‐field gel electrophoresis of DNA digested with BssH11 and Southern hybridization with cC18‐1512, DNA from the patient showed a band which was not observed in DNA isolated from either parent. As the normal size of this BssH11 fragment is 600 kb, the chromosomal breakpoint probably lies less than 600 kb away from cC18‐1512. Genes Chrom Cancer 9:57‐61 (1994). © 1994 Wiley‐Liss, Inc.
Abnormalities of chromosome 22 in pediatric meningiomas
Authors: Biegelm Jaclyn A. , Emanuel Beverly S. , Parmiter Annette H. , Sutton Leslie N. , Rorke Lucy B.
Published: February 2007

Cytogenetic studies of eight meningiomas in young children or adolescents were performed. Two tumors exhibited normal karyotypes. Two tumors from patients with bilateral acoustic neurofibromatosis demonstrated monosomy 22 as the only abnormality. Four patients had more complicated karyotypes in which one or both of the chromosomes 22 were missing or structurally altered. The most common secondary changes in these four tumors involved monosomy or structural abnormalities of Chromosome 6. These findings confirm that the primary cytogenetic changes in meningioma are similar in children and adults. Molecular analyses of pediatric meningiomas with deletions or translocations of chromosome 22 will be useful for identifying the role of chromosome 22 tumor suppressor genes in this disease. Genes Chrorn Cancer 9:81‐87 (1994). © 1994 Wiley‐Liss, Inc.
Chromosome analysis of nine osteosarcomas
Authors: Hoogerwerf W. Alexandra , Hawkins Anita L. , Griffin Constance A. , Perlman Elizabeth J.
Published: February 2007

Although recurrent chromosome abnormalities have been identified in several histologic subtypes of sarcomas, no consistent rearrangement has yet been found in osteosarcomas. Cytogenetic analyses of nine cases of osteosarcoma are reported, including seven newly diagnosed tumors and two recurrent tumors. There were seven high‐grade osteosarcomas, one periosteal osteosarcoma, and one well‐differentiated sarcoma. All tumors were studied in short‐term primary culture. Modal number ranged from near diploid to near triploid. Seven tumors had complex karyotypes with multiple structural abnormalities; two had only normal karyotypes. The retinoblastoma gene on chromosome 13 and the TP53 gene on chromosome 17 have been involved in osteosarcoma. Five tumors had loss of a whole copy of chromosome 13, and three of these also had a loss of a whole copy of chromosome 17. However, these losses were observed in the setting of numerous other chromosome loses. Numerous structural abnormalities were observed, many involving additions of unidentified material, unbalanced translocations, or deletions. Structural abnormalities with similar breakpoints involving 6q, 8q, 9q, and 14p were seen in two or three tumors each. When the tumors in this series were added to the 18 published cases, the pericentromeric regions of chromosomes 1, 3, and 14, and segments 6q 15‐21, 8q24, 9q34, 12p 13, 17p 13, and 19q 13, were found to be involved in five or more structural rearrangements. Molecular analyses of these chromosome regions may yield genes important in the pathogenesis of osteosarcoma. Genes Chrom Cancer 9:88‐92 (1994).© 1994 Wiley‐Liss, Inc.
Allelotype of uterine cancer by analysis of RFLP and microsatellite polymorphisms: Frequent loss of heterozygosity on chromosome arms 3p, 9q, 10q, and 17p
Authors: Jones Michael H. , Nakamura Yusuke , Koi Sumiko , Fujimoto Lkuno , Hasumi Katsuhiko , Kato Kyoto
Published: February 2007

Cancers in which mutations have been identified in putative tumor suppressor genes, such as the TP53 gene, the retinoblastoma (RBI) gene, the adenomatous polyposis coli (APC) gene, and the Wilms tumor (WTI) gene, frequently show loss of the corresponding allele on the homologous chromosome. To identify locations of tumor suppressor genes involved in uterine cancer, we examined loss of heterozygosity (LOH) by using genomic probes detecting RFLPs in 35 uterine cancers at 29 loci throughout the genome, and with highly informative microsatellite markers in 21 uterine cancers at nine putative or known tumor suppressor gene loci. High frequencies of allelic loss found at loci on 3p (71%), 9q (38%). 10q (35%). and 17p (35%) suggest that tumor suppressor genes involved in uterine carcinogenesis exist in these regions. There were no significant differences in frequencies of LOH between cancers of the uterine cervix and cancers of the uterine endometrium at any of the loci tested. Genes Chrom Cancer 9:119‐123 (1994).© 1994 Wiley‐Liss, Inc.
CGG‐repeat polymorphism of the BCR gene rules out predisposing alleles leading to the philadelphia chromosome
Authors: Riggins Gregory J. , Warren Stephen T. , Sherman Stephanie L , Phillips Carol N. , Stock Wendy , Westbrook Carol A.
Published: February 2007

The Philadelphia Chromosome (Ph) is associated with leukemia, most frequently of the chronic myelogenous variety. The Ph chromosome is a translocation Chromosome which gains oncogenic potential through the fusion of the ABL oncogene of chromosome 9 with the BCR gene of chromosome 22. The Ph is believed to arise from random chromosome rearrangement with a subsequent selective advantage of the malignant cell line. However, alleles may be present in the population which predispose toward this specific rearrangement. We used a highly polymorphic CGG‐repeat polymorphism within the first exon of the BCR gene to determine BCR allele frequencies among 26 leukemia patients with the Ph chromosome and 63 control individuals. Eight BCR alleles of variable CGG‐repeat length were present in both groups at statistically similar frequencies and in Hardy‐Weinberg equilibrium. We therefore concluded that there are no alleles of the BCR gene that have a major predisposing influence on the development of the ph chromosome and subsequent leukemia Genes Chrom Cancer 9:141‐144 (1994). Inc.© 1994 Wiley‐Liss, Inc.
Band 11 q 13 is nonrandomly rearranged in hibernomas
Authors: Mrœzek Krzysztof , Karakousis Constantine P. , Bloomfield Clara D.
Published: February 2007

Cytogenetic study of a short‐term culture from a hibernoma, a very rare benign proliferation of the brown fat, demonstrated a four‐break translocation t(5;7;11;17)(p14;q11.23;q13.1‐13.3;p11.2) as the sole abnormality in all analyzed cells. Complex translocations involving band 11 q 13 have also been detected in the two other published cases of hibernoma. The consistent finding of 11 q 13 rearrangements appears to distinguish hibernoma from other benign adipose tissue tumors cytogenetically and suggests that 11 q 13 changes may play an important role in hibernoma pathogenesis. Genes Chrom Cancer 9:145‐147 (1994). Inc.© 1994 Wiley‐Liss, Inc.
Loss of neurofibromin in adrenal gland tumors from patients with neurofibromatosis type I
Authors: Gutmann David H. , Cole Jeffery L. , Stone William J. , Ponder Bruce A. J. , Collins Francis S.
Published: February 2007

The neurofibromatosis type I gene encodes a protein, neurofibromin, which may function as a tumor suppressor gene product. Recent studies have demonstrated loss of neurofibromin in tumors from NFI and non‐NFI patients, including neurofibrosar‐comas, neuroblastomas and malignant melanomas. Since neurofibromin is expressed in the adrenal gland, six pheochromocy‐tomas and one adrenal cortical tumor were examined for neurofibromin expression. In all seven tumors, no neurofibromin could be detected. Furthermore, loss of heterozygosity (LOH) analysis demonstrated that in one of the pheochromocytomas, reduction to homozygosity was observed for both 17p and 17q markers while the adrenal cortical tumor demonstrated LOH for only 17q markers. The frequent LOH surrounding the NFI locus and lack of neurofibromin expression in these tumors suggest that NFI gene mutations may contribute to the development of adrenal gland neoplasms in patients with NFI. Genes Chrom Cancer 10:55–58 (1994). © 1994 Wiley‐Liss, Inc.
Chromosomal markers of immortalization in human breast epithelium
Authors: Wolman Sandra R. , Mohamed Anwar N. , Heppner Gloria H. , Soule Herbert D.
Published: February 2007

We describe a series of five immortal breast cell lines that have emerged independently from diploid cultures from two individuals. We have karyotyped representative cultures of each of these lines prior to and at intervals after immortalization. Although considerable diversity of chromosomal aberration was found among the five lines, analysis of sublines has defined the chromosomal changes common for each immortalization. These changes differed both within and between the individual patient sources. Some common alterations were noted in lines from both patients, however, including loss of the short arm of chromosome 20 and gain of I q. We suggest that genes within these chromosomal regions contribute to spontaneous immortalization of human breast epithelium. Genes Chrom Cancer 10:59–65 (1994). © 1994 Wiley‐Liss, Inc.
Localisation of the breast‐ovarian cancer susceptibility gene (BRCAI) on 17q12–21 to an interval of ⩽IcM
Authors: Smith Simon A. , Dicioccio Richard A. , Struewing Jeffery P. , Easton Douglas F. , Gallion Holly H. , Albertsen Hans , Mazoyer Sylvie , Johansson Bertil , Steichen‐Gersdorf Elisabeth , Stratton Mike , Ford Debbie , Marshall Gill , White Raymond L. , Piver M. Steven , Ponder Bruce A. J.
Published: February 2007

A breast‐ovarian cancer susceptibility gene, BRCAI, which is responsible for disease in approximately 45% of breast cancer families and most families that contain breast and ovarian cancer, has been assigned by genetic linkage to 17q12–21. Here, we report the analysis of three marker‐disease recombinants in families that contain breast and ovarian cancer, two of which strongly suggest a location for BRCAI telomeric to D17S702, a microsatellite polymorphism, and a third which suggests a location centromeric to EDH17B, the gene encoding estradiol‐17B dehydrogenase. If the interpretation of these recombinants is correct, the results localise BRCA to an interval of ⩽cM. Genes Chrom Cancer 10:71–76 (1994). © 1994 Wiley‐Liss, Inc.
Complex composition and co‐amplification of SAS and MDM2 in ring and giant rod marker chromosomes in well‐differentiated liposarcoma
Authors: Pedeutour Florence , Suijkerbuijk Ron F. , Forus Anne , Van Gaal Jose , Van De Klundert Willemijn , Coindre Jean‐Michel , Nicolo Guido , Collin Françoise , Van Haelst Urbain , Huffermann Karin , Turc‐Carel Claude
Published: February 2007

Extra abnormal chromosomes (rings and giant rods) containing chromosome 12 sequences are characteristic of well‐differentiated liposarcoma (WDLPS). By whole chromosome painting we found in 6 WDLPS that minimally 5 chromosomes had contributed to the formation of the extra abnormal chromosomes. To the constant chromosome 12 contribution, sequences were variably added from chromosomes 1, 4, and 16. Material from chromosomes 1, 4, and 12 was identified by painting in interphase nuclear projections (“blebs”) and in micronuclei consistent with the concept that blebs are precursors to micronuclei. The complexity of the mechanisms generating the extra abnormal chromosomes in WDLPS was also attested to by the diversity and, in some cases, intricacy of the patterns of fluorescence. To begin to fathom the function of the extra abnormal chromosomes we examined the amplification of genes, including SAS, MDM2, and GADDI53/CHOP, known to be in the region 12q 13–14. SAS and MDM2 demonstrated constant co‐amplification. GADD153/CHOP, which is critically rearranged in myxoid liposarcoma, was not amplified in WDLPS. Genes Chromosom Cancer 10:85–94 (1994). © 1994 Wiley‐Liss, Inc.
Non‐random chromosome rearrangements in adenoid cystic carcinoma of the salivary glands
Authors: Nordkvist Anders , Mark Joachim , Gustafsson Hans , Bang Gisle , Stenman GÖRan
Published: February 2007

The chromosomal findings in 10 adenoid cystic carcinomas (ACC) of the salivary glands are described. Clonal numerical deviations as the sole anomaly were detected in four cases and structurally rearranged stemlines and sidelines in four cases. An apparently identical t(6;9)(q23;p21) was found in two tumors; in one case the translocation was part of the abnormal stemline and in the other case it was the sole anomaly in a single variant cell. A similar or identical t(6;9)(q21‐24;p13‐23) has recently been reported in three of 15 previously published cases of ACC. The three remaining tumors with abnormal stemlines all had rearrangements of chromosome 9, including t(1;9)(q21;p21‐22), der(9)i(9)(q10)inv(9)(q12q 13), and der(X)t(X;9)(p21;p22‐23), respectively. The latter case also had a t(17;18)(p12;q11.2) that was common to both abnormal clones present in this tumor. In addition to other abnormalities, the clone with der(X)t(X;9) also showed a del(6)(q13q21). In two cases fluorescence in situ hybridization (FISH) was used for further characterization of the marker chromosomes. A survey of the present findings together with previous results from 15 ACC clearly demonstrates that rearrangements of 6q21‐24 (deletions or translocations in 11 cases), 9p13‐23 (translocations in seven cases), and 17p12‐13 (translocations in three cases) are recurrent, and often primary, in ACC, and that the t(6;9)(q21‐24;p13‐23), found in five tumors, is a non‐random, primary aberration. Genes Chromosom Cancer 10:115–121 (1994). © 1994 Wiley‐Liss, Inc.
No TP53 mutations in neuroblastomas detected by PCR‐SSCP analysis
Authors: Castresana Javier S. , Bello M. Josefa , Rey Juan A. , Nebreda Paloma , Queizàn Antonio , Garcia‐Miguel Purificatión , Pestaña Angel
Published: February 2007

We have analysed 29 neuroblastomas for TP53 mutations in exons 5 to 8 by means of the polymerase chain reaction in combination with the single‐strand conformation polymorphism technique. We could not detect any mutation. These results indicate that, in contrast to the majority of tumors so far studied, TP53 mutations do not seem to be important for the development of neuroblastomas. Genes Chromosom Cancer 10:136–139 (1994). © 1994 Wiley‐Liss, Inc.
Loss of chromosome arm 8p loci in prostate cancer: Mapping by quantitative allelic imbalance
Authors: MacGrogan Donal , Levy Alina , Bostwick David , Wagner Michael , Wells Dan , Bookstein Robert
Published: February 2007

A previous study of 18 primary or metastatic prostate cancers showed loss of genetic markers on chromosome 8; 10, or 16 in more than 50% of cases [Bergerheim USR et al. (1991) Genes Chromosom Cancer 3:215–220]. The small size and infiltrative nature of primary prostatic tumors have hindered efforts to assess allelic losses by traditional restriction fragment length polymorphism (RFLP)/Southern blotting methods. To improve the sensitivity and specificity of this analysis in early prostate cancer, we have amplified polymorphic microsatellite repeats by polymerase chain reaction (PCR), and have quantitated allelic imbalances with phosphor imaging technology. In this study, 63 primary prostate tumors and matched benign tissues obtained by radical prostatectomy were examined at 28 genetic loci on chromosome 8, all but five of which were located on the short arm. Twenty‐nine (46%) of the 63 cases showed loss of at least one locus. Multiple adjacent loci, usually including the LPL and MSR genes in 8p22, were lost in 28 cases. In 10 of these, losses were observed at all informative loci on the p arm. In another 15 tumors, losses were restricted to subregions of the p arm by loci retained either distally toward the p terminus or proximally at the 8p 12–8p21 border, or both. In three tumors, two discrete regions of loss were observed within 8p, separated by several retained loci. Allelic loss of 8p loci was associated with higher tumor grade. These data are complementary to previous reports of allelic deletions in colorectal, hepatocellular, and non‐small cell lung cancers and suggest the existence of one or more pleotropic tumor suppressor genes on 8p. Genes Chromosom Cancer 10:151–159 (1994). © 1994 Wiley‐Liss, Inc.
Detection of DNA amplification in 17 primary breast carcinomas with homogeneously staining regions by a modified comparative genomic hybridization technique
Authors: Muleris Martine , Almeida Anna , Gerbault‐Seureau Michèle , Malfoy Bernard , Dutrillaux Bernard
Published: February 2007

A modified comparative genomic hybridization (mCGH) technique was applied to a series of 17 primary breast carcinomas in which cytogenetic study (CG) demonstrated the presence of homogeneously staining region(s), suggesting the occurrence of DNA amplification. mCGH demonstrated recurrent amplifications of the whole chromosome arms 8q (9 times) and I q (7 times) and of DNA loci in the following bands: 11 q 13 (6 times), 9p 13 and 17q21.1 (4 times), I q21.1 and 16p 11.2 (3 times), and 8q22, 8q24.1, 10q22, 15q26, 17q23, and 20q 13.3 (twice). Amplification of whole chromosome arms is likely to have resulted from unbalanced translocations or isochromosomes, whereas amplifications of smaller chromosomal segments probably arose through real DNA amplification processes. In all tumors but one, more than one amplified locus was detected. The fact that many chromosomal sites were involved suggests that the process of amplification is complex and that many genes are potential targets. Genes Chromosom Cancer 10:160–170 (1994). © 1994 Wiley‐Liss, Inc.
t(1;19) without detectable E2A rearrangements in two t(14; 18)‐positive lymphoma/leukemia cases
Authors: Wlodarska Iwona , Stul Michel , De Wolf‐Peeters Chris , Verhoef Gregor , Mecucci Cristina , Cassiman Jean‐Jacques , Van Den Berghe Herman
Published: February 2007

Translocation t(1;19)(q23;p13) plays a crucial role in the pathogenesis of childhood pre‐B cell leukemia and results in the formation of a fusion gene E2A‐PBXI that encodes a hybrid transcription factor with oncogenic potential. Here we describe two cases, one follicular lymphoma and one acute lymphoblastic leukemia/lymphoma, characterized by a complex karyotype including t(14;18), t(8;14), as well as t(1;19). Molecular studies in both cases failed to show rearrangements of the E2A gene. These results suggest that the t(1;19) found as a secondary chromosome change in t(14;18)‐positive lymphoma/leukemia might be a molecular variant of the t(1;19) that is typical of childhood pre‐B cell leukemia. Genes Chromosom Cancer 10:171–176 (1994). © 1994 Wiley‐Liss, Inc.
Chromosome abnormalities in hairy cell leukaemia variant
Authors: Brito‐Babapulle Vasantha , Matutes Estela , Oscier David , Mould Sarah , Catovsky Daniel
Published: February 2007

We describe chromosome abnormalities in 6 patients with hairy cell leukaemia (HCL) variant, a rare B‐cell disorder with clinical and laboratory features intermediate between HCL and B‐prolymphocytic leukaemia (B‐PLL). All but one had marked splenomegaly and a raised white blood cell count (median 40 × 109/l) with over 80% nucleolated hairy cells. These cells had a B‐cell immunophenotype distinct from that of typical HCL. All patients but one are alive with stable disease with a median follow‐up of 60 months. Numerical chromosome changes included loss of chromosomes 2, 3, 4, 6, 10, 19, 21, and X. Three cases had translocations involving the immunoglobulin gene regions: t(14;17)(q32;q11), t(14;22)(q32;q11), and t(2;8)(p11.12;q24). Immunocytochemistry demonstrated the presence of the MYC protein in cells from the case with t(2;8) but not in two others. Other structural abnormalities included t(3;10)(q27;q22) and t(3;12)(q27;q13) in the same patient, der(17)t(7;10;17) (p11;q27;q22), t(1;3)(q25;p21), t(8;21)(p12;q11), t(17;21)(p11;p11), del(6)(q15), del(7)(q34), and del(14)(q24). Genes Chromosom Cancer 10:197–202 (1994). © 1994 Wiley‐Liss, Inc.
Cytogenetic study of angiosarcoma of the breast
Authors: Gil‐Benso Rosario , López‐Ginés Concha , Soriano Pilar , Almenar Sergio , Vazquez Carlos , Llombart‐Bosch Antonio
Published: February 2007

Angiosarcoma of the breast is quite rare, and the development of cutaneous angiosarcoma after segmental mastectomy and radiation therapy is even less common. A cytogenetic analysis of a mammary angiosarcoma arising in a breast after previous irradiation and segmental mastectomy for infiltrating ductal carcinoma revealed multiple clonal rearrangements involving chromosomes X, 1, 2, 3, 4, 5, 6, 7, 8, 9, 15, 17, 20, and 22. No cytogenetically analyzed angiosarcomas of the breast have been reported before. Genes Chromosom Cancer 10:210–212 (1994). © 1994 Wiley‐Liss, Inc.
Optimizing comparative genomic hybridization for analysis of DNA sequence copy number changes in solid tumors
Authors: Kallioniemi Olli‐P. , Kallioniemi Anne , Piper Jim , Isola Jorma , Waldman Fred M. , Gray Joe W. , Pinkel Dan
Published: February 2007

Comparative genomic hybridization (CGH) is a powerful new method for molecular cytogenetic analysis of cancer. In a single hybridization, CGH provides an overview of DNA sequence copy number changes (losses, deletions, gains, amplifications) in a tumor specimen and maps these changes on normal chromosomes. CGH is based on the in situ hybridization of differentially labeled total genomic tumor DNA and normal reference DNA to normal human metaphase chromosomes. After hybridization and fluorescent staining of the bound DNAs, copy number variations among the different sequences in the tumor DNA are detected by measuring the tumor/normal fluorescence intensity ratio for each locus in the target metaphase chromosomes. CGH is in particular useful for analysis of DNA sequence copy number changes in common solid tumors where high‐quality metaphase preparations are often difficult to make, and where complex karyotypes with numerous markers, double minutes, and homogeneously stained chromosomal regions are common. CGH only detects changes that are present in a substantial proportion of tumor cells (i.e., clonal aberrations). It does not reveal translocations, inversions, and other aberrations that do not change copy number. At present, CGH is a research tool that complements previous methods for genetic analysis. CGH will advance our understanding of the genetic progression of cancer and highlight important genomic regions for further study. Direct clinical applications of CGH are possible, but will require further development and validation of the technique. We describe here our recent optimized procedures for CGH, including DNA labeling, hybridization, fluorescence microscopy, digital image analysis, data interpretation, and quality control, emphasizing those steps that are most critical. We will also assess sensitivity and resolution limits of CGH as well as discuss possible future technical improvements. Genes Chromosom Cancer 10:231–243 (1994). © 1994 Wiley‐Liss, Inc.
TP53 mutations are frequent in malignant NFI tumors
Authors: Legius Eric , Dierick Herman , Wu Rina , Hall Bryan K. , Marynen Peter , Cassiman Jean‐Jacques , Glover Thomas W.
Published: February 2007

Neurofibromatosis type I (NFI) is a common autosomal dominant disorder with an increased risk for developing benign and malignant tumors. The NFI gene has been cloned and maps to 17qII.2, and the gene product acts as a tumor suppressor gene. Here we analyzed the role of mutations in TP53 in four malignant NFI tumors. Mutations were found in 3 out of 4 tumors. One of these mutations is a common missense mutation in codon 278 in one of the previously identified hot spots for mutations. The two other are hitherto unreported mutations, including a splice mutation of exon 3 and a nonsense mutation in exon 4. In addition, these four tumors also showed loss of heterozygosity (LOH) for markers on chromosome 17 in the region of TP53. Malignant NFI tumors are initiated by a somatic inactivation of the second NFI allele. Tumor progression, however, occurs by accumulation of additional genetic abnormalities, such as homozygous inactivation of TP53, as demonstrated in this paper. Genes Chromosom Cancer 10:250–255 (1994). © 1994 Wiley‐Liss, Inc.
Submicroscopic deletions of 3p sequences in pleomorphic adenomas with t(3;8)(p21;q12)
Authors: Sahlin Pelle , Mark Joachim , Stenman Göran
Published: February 2007

A subgroup of benign pleomorphic adenomas of the salivary glands is characterized by translocations, or on rare occasions deletions, with breakpoints at 3p2I. We have applied restriction fragment length polymorphism (RFLP) analysis to assess the frequency of allelic losses at four different loci located within 3p2I p25 in 35 pleomorphic adenomas, 18 of which were also karyotyped. Parallel analysis of constitutional and tumor DNAs in informative tumors revealed that all patients retained heterozygosity in their tumor DNA at the D3S2 and RAFI loci. Among the 29 tumors informative for THRB three showed loss of heterozygosity (LOH). All three tumors had a t(3;8)(p2I;qI2). Of the 23 tumors informative for D3FI5S2, one showed LOH. This tumor also had a t(3;8)(p2I;qI2). To further map the deletions in relation to the 3p2I translocation breakpoint, we also sublocalized the THRB locus. Using in situ hybridization we assigned the gene to 3p24.I‐.3. The fact that none of the tumors with loss of 3p alleles showed cytogenetic evidence of deletions indicates that the losses are submicroscopic, probably interstitial, and in most cases distal to the 3p2I breakpoint. This was confirmed in one case with loss of a THRB allele where both proximal (D3FI5S2) and distal (RAFI) markers retained heterozygosity. Our results suggest that deletion of 3p sequences might be of progressional importance in a subset of pleomorphic adenomas with t(3;8)(p2I;qI2). Genes Chromosom Cancer 10:256–261 (1994). © 1994 Wiley‐Liss, Inc.
Simple numeric abnormalities as primary karyotype changes in ovarian carcinoma
Authors: Thompson Floyd H. , Liu Yun , Emerson Julia , Weinstein Ronald , Makar Rosemary , Trent Jeffrey M. , Taetle Raymond , Alberts David S.
Published: February 2007

Simple near‐diploid karyotypes in ovarian cancer may indicate either primary alterations related to tumor pathogenesis or abnormalities associated with early tumor progression. We have identified a series of 13 epithelial ovarian tumors with very simple karyotypes. Specifically, these karyotypes were near‐diploid and displayed numeric abnormalities alone or combined with one or two structural alterations. The present series includes samples from 10 patients with newly diagnosed adenocarcinomas and 3 patients having borderline malignancies. Recurrent numeric abnormalities were identified and included 9/13 cases (69%) with + 12, eight cases (62%) with + 8, five cases (38%) with + 7, three cases (23%) each with + 3 or + 5, and two cases (15%) with ‐X, Five cases in this series displayed certain numeric abnormalities (+ 12, + 7, and ‐X) as the sole anomalies, thereby qualifying as primary karyotype changes. Of the 6 cases with structural abnormalities, 4 involved chromosome 19, 2 involved chromosome I, and the remaining abnormalities or translocation partners involved other chromosomes. These findings indicate that some numeric abnormalities are primary karyotype alterations in patients with malignant epithelial ovarian tumors and that chromosome 19 may be preferentially involved in structural rearrangements during early tumor progression. Genes Chromosom Cancer 10:262–266 (1994). © 1994 Wiley‐Liss, Inc.
Putative “MDR enhancer” is located on human chromosome 20 and not linked to the MDRI gene on chromosome 7
Authors: Germann Ursula A. , Schoenlein Patricia V. , Zimonjic Drazen B. , Popescu Nicholas C. , Pastan Ira , Gottesman Michael M.
Published: February 2007

The physiologic expression of the human multidrug resistance MDRI gene product P‐glycoprotein is controlled in a tissue‐ and cell‐specific manner, but the regulatory mechanisms have not been characterized in great detail. Studies by Kohno et al. [(1990) J Biol Chem 265:19690–19696] suggested that a tissue‐specific enhancer element located approximately 10 kb upstream from the major MDRI transcription start site may act to increase the levels of transcription in cultured adrenal and kidney cells. Using this putative “MDR enhancer” as a probe, we isolated a 14 kb DNA fragment from a genomic DNA library prepared from human fetal liver. The restriction map and partial nucleotide sequence of this DNA fragment were consistent with the previously described data obtained for a similar piece of genomic DNA derived from human placenta by Kohno et al. (ibid.). Pulsed‐field gel electrophoresis of large genomic DNA fragments, however, showed that the DNA sequences, including the putative “MDR enhancer,” were not linked to the MDRI gene. Fluorescence in situ hybridization analysis revealed that this enhancer‐like element is located on chromosome 20 at band q13.1 and is, therefore, distinct from the MDR locus on chromosome 7, band q21.1. Thus, this putative regulatory element does not modulate the tissue specificity of expression of the MDRI gene in vivo, but may play a role in the regulation of expression of another, so far unknown gene. Genes Chromosom Cancer 10:267–274 (1994). © 1994 Wiley‐Liss, Inc.
Cytogenetic analysis of a choroid plexus papilloma
Authors: Punnett Hope H. , Tomczak Ewa Z. , De Chadarevian Jean‐Pierre , Kanev Paul M.
Published: February 2007

We report the cytogenetic analysis of a choroid plexus papilloma, a benign tumor, with a modal number of 56 chromosomes. In our review of the few reported karyotypes of choroid plexus tumors, we found no predictive relationship between the karyotype and the pathologic diagnosis or outcome. Genes Chromosom Cancer 10:282–285 (1994). © 1994 Wiley‐Liss, Inc.
Analysis of mutations in the SCH gene in schwannomas
Authors: Bijlsma Emilia K. , Merel Philippe , Bosch D. Andries , Westerveld Andries , Delattre Olivier , Thomas Gilles , Hulsebos Theo J. M.
Published: February 2007

Schwannomas are benign tumors of cranial, spinal, and other nerve sheaths that develop sporadically or are inherited as part of neurofibromatosis type 2 (NF2). The NF2 gene (SCH) on chromosome 22 has recently been identified and shown to be inactivated by mutation and allele loss in some schwannomas. However, only limited regions in the SCH coding region were examined for mutations. We have extended these studies by screening virtually all coding sequences of the SCH gene (95% coverage) and adjacent splice site sequences for the presence of mutations in 48 schwannomas. All tumors (34 vestibular schwannomas and 14 schwannomas of other locations) were additionally characterized for allele loss on chromosome 22. By PCR‐DGGE screening of the 16 known exons of the SCH gene, 22 mutations were found. Most of these give rise to a premature stop codon and are expected to result in the synthesis of a truncated gene product (schwannomin). Although there was no apparent hotspot for mutations, 16 of the 22 mutations occurred in the first eight exons or adjacent splice site sequences of the SCH gene. In several vestibular as well as other schwannomas loss of one SCH allele and mutational inactivation of the second allele were identified in the same tumor. Our data indicate that the SCH gene is implicated in the development of schwannomas of all locations in the nervous system.
Molecular heterogeneity at the breakpoints of smaller 20q deletions
Authors: Hollings Peter E.
Published: February 2007

Deletions of the long arm of chromosome 20 [del(20q)] are recurring abnormalities in patients with myeloid disorders. Although variable in size, these deletions are usually interstitial. With the object of defining a commonly deleted region for smaller 20q deletions, we used quantitative Southern blot analysis complemented by restriction fragment length polymorphism (RFLP) analysis to determine the copy number at 15 loci spanning 20q. The proximal breakpoints of three such deletions were found to separate HCK and the growth hormone releasing factor (GHRF) locus near the centromeric boundary of band 20q 11.2. The distal breakpoints were localized to the vicinity of the D20S22 locus in band q13.1.A candidate tumor suppressor gene, RBL2, and the SRC oncogene were both located within the commonly deleted region. Six loci in terminal region q13.2‐q13.3 were conserved on these del(20q) chromosomes, thereby confirming that the deletions were interstitial. Molecular heterogeneity at one and possibly both deletion breakpoints rules out the pathological involvement of loci at these sites. Instead, loss of a tumor suppressor locus from within the commonly deleted region may contribute to deregulated hemopoiesis.
Consistent chromosomal losses in head and neck squamous cell carcinoma cell lines
Authors: Sreekantaiah Chandrika , Rao Pulivarthi H. , Xu Li , Sacks Peter G. , Schantz Stimson P. , Chaganti R. S. K.
Published: February 2007

Clonal chromosomal abnormalities were characterized in nine cell lines established from squamous cell carcinomas of the head and neck. Aneuploidy was a common feature; one cell line was near‐diploid, three were near‐triploid, four were near‐tetraploid, and one cell line showed extensive variation in chromosome numbers. Consistent numerical abnormalities included loss of the sex chromosomes in six cell lines, losses of chromosomes 2 and 21 in six and five cell lines, respectively, and gain of chromosome 20 in five cell lines. Recurrent structural rearrangements included del(10)(q22‐q26) (seven cell lines), i(5)(p10) (six cell lines), i(8)(q10) (six cell lines), add(19)(q13) (six cell lines), del(4)(q21‐q31.3) (five cell lines), i(3)(q10) (four cell lines), del(12)(p11.1‐p12) (four cell lines), and add (18)(q21‐q23) (four cell lines). Other changes were noted in lower frequencies. Loss of specific regions on chromosomes 2, 3p, 4q, 5q, 8p, 10q, 12p, 18q, 19q, and 21 suggests that they may represent sites of putative tumor suppressor genes, loss of which may play a role in the pathogenesis of squamous cell carcinomas of the head and neck. Alternatively, gain of chromosomal region 3q, 5p, and 8q due to isochromosome formation suggests that more than one mechanism is involved in malignant transformation. Cytogenetic evidence of gene amplification was found in two cell lines; as an hsr(11)(q 13) in one and as dmins in the other. The clonal karyotypes of four cell lines were compared with those of their respective primary tumors. In all cell lines, clonal evolution had occurred, with loss of some rearrangements present in the primary tumors or the gain of additional abnormalities.
The heregulin gene can be included in the 8p12 amplification unit in human breast cancer
Authors: Adélaïe José , Penault‐Llorca Frédérique , Dib Amel , Yarden Yosef , Jacquemier Jocelyne , Birnbaum Daniel
Published: February 2007

The Heregulin (HGL) gene, encoding a ligand for a member of the ERBB receptor family, is located at 8p 12‐p22, in or close to a region frequently amplified in breast carcinoma. Amplification of HGL was detected in three of 83 (3.6%) cases of breast tumors. No overexpression of the gene was observed in the amplified tumors. This and the low incidence of amplification suggest that HGL is not the key gene of the 8p 12 amplification but may be used as a marker of large amplification units.
Identification, molecular cloning, and characterization of the chromosome 12 breakpoint cluster region of uterine leiomyomas
Authors: Schoenmakers Eric F. P. M. , Mols Raf , Wanschura Sylke , Kools Patrick F. J. , Geurts Jan M. W. , Bartnitzke Sabine , Bullerdiek Jörn , Berghe Herman Van Den , Van Ven Wim J. M. De
Published: February 2007

Recent molecular cytogenetic analysis of uterine leiomyoma cell lines with chromosome 12 aberrations has indicated that their chromosome 12 breakpoints map between linkage locus D12S8 and the CHOP gene. Here, we report fluorescence in situ hybridization (FISH) and molecular cloning studies of the chromosome 12 breakpoints in a panel of seven such uterine leiomyoma cell lines; five with the frequently observed t(12; 14)(q15;q24), one with t(12;15)(q15;q24), and one with ins(12;11)(q14;q21 qter). Directional chromosome walking studies starting from D12S8 and the CHOP gene resulted in the isolation of a relatively large number of overlapping YAC clones, including Y5355 (465 kbp), Y7673 (360 kbp), and Y9899 (275 kbp). In total, the inserts of these three YAC clones span an 800 kbp long and presumably contiguous stretch of human genomic DNA. All chromosome 12 breakpoints of the uterine leiomyoma cell lines studied were found by FISH analysis to be mapping within a 445 kbp subfragment of this region and, furthermore, to be dispersed over a DNA region which is at least 150 kbp in size. The chromosome 12 breakpoint of t(12;14)(q15;q24) in uterine leiomyoma cell line LM‐30.1/SV40 was tentatively mapped within the 60 kbp region between YAC clones Y9899 and Y5355. From this 60 kbp region and close to sequencetagged site RM99, we isolated probe pRM 118‐A, which showed in Southern blot analysis that it detected a rearrangement in LM‐30.1/SV40 DNA, and generated restriction maps of the normal and rearranged genomic DNA regions detected with this probe. Finally, we molecularly cloned part of one of those rearranged DNA fragments using a vectorette‐PCR‐based technique and demonstrated that it consisted of 12q13‐q15 sequences fused to DNA sequences derived from 14q23‐24 and most likely represented the translocation junction on der(14) in LM‐30.1/SV40 cells. Our studies strongly suggest that we have identified and isolated the uterine leiomyoma cluster region of chromosome 12 breakpoints, which we designate ULCR12, and molecularly cloned and characterized the der(14) translocation junction in cells derived from a uterine leiomyoma carrying the frequently observed t(12;14)(q15;q24).
Genetic alterations in localized prostate cancer: Identification of a common region of deletion on chromosome arm 18q
Authors: Latil Alain , Baron Jean‐Christophe , Cussenot Olivier , Fournier Georges , Soussi Thierry , Boccon‐Gibod Laurent , Duc Alain Le , Rouëssé Jacques , Lidereau Rosette
Published: February 2007

Accumulation of mutations in oncogenes and tumor suppressor genes transforms a normal cell into a malignant cell by allowing it to escape from normal control of growth. In prostate tumorigenesis, the current model envisages specific mutations of the TP53 tumor suppressor gene and loss of loci, detected by loss of heterozygosity (LOH), on chromosome arms 8p, 10q, 16q, and 18q. In order to determine if alterations frequently found in other adenocarcinomas (breast, ovarian, gastric, colorectal), including losses of genetic material from chromosome arms 1p, 3p, 7q, 8p, 11p, 17p, 17q, and 18q, are also involved in prostate cancer, we examined 20 localized early‐stage prostate tumors. We detected no mutations of the TP53 gene. Allelic losses were found from 7q (33%), 8p (50%), 10q (20%), and 18q (33%). Furthermore, as the first step toward isolating tumor suppressor genes on 18q, we used six polymorphic markers and identified a small common deleted region between the chromosome 18 centromere and the D18S19 locus.
Comparative genomic hybridization, allelic imbalance, and fluorescence in situ hybridization on chromosome 8 in prostate cancer
Authors: Cher Michael L. , Macgrogan Donal , Bookstein Robert , Brown James A. , Jenkins Robert B. , Jensen Ronald H.
Published: February 2007

Due to problems with primary tumor cell culture, conventional cytogenetics has yielded little insightful information on chromosomal alterations in prostate cancer. The primary aim of this study was to define the ability of comparative genomic hybridization (CGH) to detect and map genetic deletions in prostate tumors. A secondary aim was to apply multiple assays to individual tumors as a means of deciphering the mechanisms of genetic alterations in prostate cancer. CGH results were compared with allelic imbalance measurements at 29 distinct loci on chromosome 8 in 18 specimens (17 malignant and 1 benign). CGH detected no changes in cases where all informative PCR/RFLP loci were retained and detected all p arm deletions consisting of at least two loci. We estimate that in this study, the smallest deletions detected by CGH were approximately 20‐30 cM. Physical mapping of subchromosomal arm deletions by CGH correlated well with allelic imbalance mapping by PCR/RFLP: The data agreed at 88% of loci on 8p and 92% of loci on 8q. Fluorescence in situ hybridization (FISH) with multiple centromere probes and DNA content flow cytometry (FCM) also was performed on selected specimens. FISH revealed two cases of chromosome 8 aneusomy. In these two cases and three others, CGH showed simultaneous p arm deletion and q arm gain, suggesting isochromosome 8q formation. Together, these data suggested that simple chromosomal aberrations were responsible for allelic losses on 8p and allelic gains on 8q in a significant number of prostate tumors. We also used CGH to examine relative DNA sequence copy number throughout the genome. Changes frequently associated with 8p loss include gains of 8q and losses of 13q, 16p, 16q, 17p, 17q, 20q, and Y. Cases with 8p loss exhibited five times the number of alterations as did cases without 8p loss.
Delineation of two distinct deleted regions on chromosome 9 in human non‐melanoma skin cancers
Authors: Quinn Anthony G. , Sikkink Stephen , Rees Jonathan L.
Published: February 2007

The mapping of the naevoid basal cell carcinoma syndrome (NBCCS) and the Ferguson‐Smith syndrome to the same region on chromosome arm 9q has led to speculation that the two conditions may reflect different mutations within the same gene. Loss of heterozygosity of 9q alleles in both familial and sporadic basal cell carcinomas (BCCs) suggests that the NBCCS gene on 9q is acting as a tumour suppressor gene. Although LOH of 9q markers has not been studied in squamous cell neoplasms from patients with the Ferguson‐Smith syndrome, chromosome 9 allele loss has been reported in sporadic squamous cell carcinomas (SCCs) of the skin. In order to characterise further the deleted region on chromosome 9 in BCCs and SCCs of the skin we have examined a series of non‐melanoma skin cancers using a panel of highly informative microsatellite markers. Forty‐four BCCs and 49 SCCs were studied. Loss of heterozygosity of one or more 9q markers was seen in 33 of the 44 BCCs. Only 4 of the 33 BCCs with 9q loss showed loss of 9p markers. Twenty‐two BCCs showed loss of all informative 9q markers. Partial or interstitial 9q deletions were seen in 5 BCCs, and in 3 of these 5 BCCs the breakpoint occurred within the currently defined NBCCS locus. Chromosome 9 loss was seen in 16 of 49 SCCs. In contrast to the low frequency of 9p loss in BCCs, LOH of 9p markers was a common finding in SCCs, occurring in 15 of the 16 SCCs with chromosome 9 loss. In 5 SCCs 9p loss occurred with retention of 9q alleles. The different patterns of chromosome 9 loss in BCCs and SCCs and the failure to detect loss of markers at the Ferguson‐Smith/NBCCS locus in 5 of 7 informative SCCs with partial chromosome 9 losses suggest that the targets for allelic deletion on chromosome 9 in BCCs and SCCs are different.
Molecular cloning of a t(11; 14)(q13;q32) translocation breakpoint centromeric to the BCLI‐MTC
Authors: Galiègue‐Zouitina Sylvie , Collyn‐d'Hooghe Maud , Denis Claude , Mainardi Anne , Hildebrand Marie‐Paule , Tilly Hervé , Bastard Christian , Kerckaert Jean‐Pierre
Published: February 2007

In B‐cell malignancies, the t(11;14)(q13;q32) at the 11q13 BCLI locus is characterized by a scattering of breakpoint sites along a 100 kb genomic region, between the BCLI major translocation cluster (MTC) and the PRADI (also termed cyclin DI or CCNDI) gene. Recently, the 11q13 breakpoint region was extended on both sides, centromeric to the MTC and telomeric to PRADI. We report here the molecular cloning of a new t(11;14) breakpoint site, 20 kb centromeric to the MTC, from a patient with prolymphocytic leukemia. We subcloned a non‐repetitive DNA fragment near the breakpoint and mapped this new 11q13 probe (pHOIIc) relative to already identified breakpoint sites, using long‐ and short‐range physical mapping within the BCLI locus. Rearrangements in the BCLI locus are associated with deregulation of the PRADI gene, which is often overexpressed, particularly in mantle‐cell malignancies. The detectable but weak PRADI expression in the case we present suggests that this breakpoint centromeric to the MTC still lies inside the BCLI locus boundaries. We think that attention should be focused on this region centromeric to the BCLI‐MTC, where the investigation of previously unidentified translocations may increase understanding of the PRADI gene deregulation in t(11;14) associated pathologies.