摘要:

AbstractIn order to ascertain the frequency and distribution of isochromosomes in neoplasia, we surveyed the cytogenetic data from 20,007 tumors with clonal chromosome aberrations reported in the literature. Tumor types for which at least 50 cases with acquired aberrations and 10 cases with isochromosomes had been reported were selected, yielding a total of 18, 160 neoplasms. Of these, 1,792 cases (9.9%) displayed a total of 2,014 isochromosomes. The 9 most common isochromosomes (detected in at least 50 cases) were, in decreasing order of frequency, i(17q), i(8q), i(lq), i(12p), i(6p), i(7q), i(9q), i(5p), and i(21q). The frequency of isochromosomes varied among the different tumor types, with the highest incidence in germ cell neoplasms (60%) and the lowest in chronic myeloproliferative disorders (2.3%). Also, the spectrum of isochromosomes differed among the neoplasms. The most common isochromosomes in the different tumor types were i(I Iq), i(I7q), and i(2Iq) in acute myeloid leukemia; i(9q), i(I7q), and i(22q) in chronic myeloid leukemia; i(I7q) in chronic myeloproliferative disorders; i(X)(qI3), i(I7q), and i(2Iq) in myelodysplastic syndromes; i(7q), i(9q), and i(I7q) in acute lymphoblastic leukemia; i(Iq), i(7q), i(8q), and i(I7q) in chronic lymphoproliferative disorders; i(Iq), i(6p), i(9p), i(I7q), and i(2Iq) in Hodgkin's disease; i(Iq), i(6p), and i(7q) in non‐Hodgkin's lymphoma; i(Iq), i(8q), and i(I7q) in adenocarcinoma; i(Iq), i(3q), i(5p), and i(8q) in squamous cell carcinoma; i(5p), i(8q), and i(IIq) in transitional cell carcinoma; i(Iq), i(7q), and i(I7q) in Wilms' tumor, i(Iq), i(I2p), and i(I7q) in germ cell neoplasms; i(Ip), i(Iq), i(6p), and i(I7q) in sarcoma; i(5p), i(6p), i(7p), and i(2Iq) in mesothelioma; i(lq), i(6p), and i(I7q) in malignant neurogenic neoplasms; i(Iq), i(6p), and i(I7q) in retinoblastoma; and i(Iq), i(6p), and i(8q) in malignant melanoma. GenesChromosom Cancer10:221–230 (1994). © 1994 Wiley‐Lis

ISSN:1045-2257    

DOI:10.1002/gcc.2870100402

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractComparative 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 labeledtotal genomic tumorDNA and normal reference DNA tonormalhuman 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 Cancer10:231–243 (1994). © 1994 Wiley‐Lis

ISSN:1045-2257    

DOI:10.1002/gcc.2870100403

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractEight patients with myeloid disorders characterised by a karyotype including apparent monosomy or partial monosomy 7, in the presence of a ring or marker chromosome, were investigated by fluorescence in situ hybridisation (FISH) with a chromosome 7 centromere‐specific probe and anAlu‐PCR derived chromosome 7 paint. In 4 of 5 cases a ring chromosome was shown to be of chromosome 7 origin; in one of these the apparent ring was shown to consist solely of chromosome 7 centromeric material, and in the fifth case the ring was derived from chromosome 18. In three cases monosomy 7 had arisen during the course of karyotype evolution and was clearly not the primary cytogenetic abnormality. One further case demonstrated fragmentation and cryptic translocation of chromosome 7 material. In the last case a chromosome described as der(I)t(I;7)(p II;pII) was redefined as dic(I;7)(pII;qII). The application of FISH has enabled a more accurate characterisation of chromosome abnormalities, and extended studies of this type may eventually lead to more precise prognostic groups defined by karyotype.Genes Chromosom Cancer10:244–249 (1994). © 1994 Wiley‐L

ISSN:1045-2257    

DOI:10.1002/gcc.2870100404

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractNeurofibromatosis type I (NFI) is a common autosomal dominant disorder with an increased risk for developing benign and malignant tumors. TheNFIgene 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 inTP53in 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 ofTP53.Malignant NFI tumors are initiated by a somatic inactivation of the secondNFIallele. Tumor progression, however, occurs by accumulation of additional genetic abnormalities, such as homozygous inactivation ofTP53, as demonstrated in this paper.Genes Chromosom Cancer10:250–255 (1994). © 1994 Wiley‐Liss,

ISSN:1045-2257    

DOI:10.1002/gcc.2870100405

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractA 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 andRAFIloci. Among the 29 tumors informative forTHRBthree 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 theTHRBlocus. 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 aTHRBallele 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 Cancer10:256–261 (1994). © 1994 Wiley‐Lis

ISSN:1045-2257    

DOI:10.1002/gcc.2870100406

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractSimple 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

ISSN:1045-2257    

DOI:10.1002/gcc.2870100407

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe physiologic expression of the human multidrug resistanceMDRIgene 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 majorMDRItranscription 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 theMDRIgene. 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 theMDRlocus on chromosome 7, band q21.1. Thus, this putative regulatory element does not modulate the tissue specificity of expression of theMDRIgene 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)

ISSN:1045-2257    

DOI:10.1002/gcc.2870100408

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe short arm of chromosome Ip is the most frequently altered chromosome segment in neuroblastoma. The alterations, mainly deletions, are thought to be indicative of the presence of a tumor suppressor gene. To further refine the chromosome localization of this gene, we have studied paired constitutional and tumor DNA from a series of 60 patients with neuroblastoma at 2 minisatellite and 23 microsatellite loci dispersed along the short arm of chromosome I. Twenty‐two cases (37%) demonstrated loss of heterozygosity (LOH) at one or more loci on 1p. Surprisingly, the pattern of LOH enabled the identification of two distinct consensus regions of deletions. In agreement with previous reports, one region mapped to the distal short arm of chromosome 1. The other region was localized more proximally on 1p. Deletions observed in tumors involve either one or both of these regions. We show that the correlation betweenNMYCamplification and 1p deletion is limited to the deletions which involve the proximal region either alone or together with the distal region. These results suggest that two tumor suppressor genes on lp might be involved in the development of neuroblastoma. Finally, we show that somatic mutations at microsatellite loci, frequently observed in other types of cancer, are rare events in neuroblastoma.Genes Chromosom Cancer 10:275–281 (1994). © 1994 Wiley‐Lis

ISSN:1045-2257    

DOI:10.1002/gcc.2870100409

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractWe 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 Cancer10:282–285 (1994). © 1994 Wiley‐Liss,

ISSN:1045-2257    

DOI:10.1002/gcc.2870100410

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractWe have used fluorescence in situ hybridisation (FISH) with a series of yeast artificial chromosome (YAC) clones that map to the long arm of chromosome 6 (6q) to define the region(s) of deletion in seven cases of non‐Hodgkin's lymphoma (NHL), in which a deletion of 6q had been detected by conventional cytogenetics. The FISH analysis detected two regions of deletion: (i) A proximal region flanked byM6PI(6q 14–15) andFYN(6q21), containing D6S246, which was missing in all seven cases. This locus was also found to be deleted in all six cases of acute lymphoblastic leukaemia (ALL) studied previously, (ii) A second region of 6q, which was distal to 6q23.1 (D6S238) and includedESR(6q25.l) and D6S281 (6q27), which was shown to be present in all our cases of ALL, was found to be deleted in 4 of the 7 cases of NHL. Our results support the suggestion that tumour suppressor genes, involved in the pathogenesis of lymphoid malignancies, may be present within these regions.Genes Chromosom Cancer 10:286–288 (1994).© 1994 Wiley‐L

ISSN:1045-2257    

DOI:10.1002/gcc.2870100411

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY