摘要:

AbstractLoss of the Y chromosome in bone marrow (BM) cells is a normal age‐associated event. Y chromosome loss is also observed in the Philadelphia chromosome (Ph) positive BM cells of some patients with chronic myeloid leukemia (CML) in chronic phase, but at a younger age than in normal individuals. While the significance of loss of the sex chromosome in normal males is uncertain, ‐Y marrow cells are not believed to be of clonal origin. However, because CML is a clonal disease, CML sub‐populations with Y loss may constitute a disease‐related sub‐clone. We used a PCR‐amplified yeast artificial chromosome containing theBCRgene region for single color interphase analysis ofBCRrearrangement by fluorescence in situ hybridization (FISH). Then, using two color FISH, with one fluorochrome detecting theBCRgene region and the other detecting Y chromosome repeat sequences, we surveyed peripheral and BM Y loss in both normal Ph‐ (BCRnot disrupted) and CML Ph+ (BCRrearranged) interphase nuclei of two patients with Y loss in Ph positive cells observed by metaphase analysis. ‐Y was seen in a proportion of Ph+ cells in both cases, and the proportion matched that seen in Ph‐ cells, indicating that Y loss is probably sporadic in both normal and CML populations, and that the propensity for Y loss in normal BM cells may be a phenotype that can be retained by malig

ISSN:1045-2257    

DOI:10.1002/gcc.2870110302

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

年代:1994

数据来源: WILEY

摘要:

AbstractRhabdoid tumor of the kidney (RTK) is associated with tumors of the central nevous system (CNS) in approximately 15% of cases. We describe the clinical features, histologic and cytogenetic findings, and molecular analysis of renal and CNS tumors from the same patient. The histology of the renal tumor was consistent with rhabdoid tumor. The CNS tumor was a primitive neuroectodermal tumor (PNET). The karyotype of the RTK was normal male. The PNET of the brain demonstrated monosomy 22 as the only cytogenetic abnormality, similar to reported cases of malignant rhabdoid tumor of the brain, but dissimilar to nonrandom cytogenetic findings in other CNS PNETs. Molecular cytogenetic and DNA marker studies confirmed loss of chromosome 22 in this patient's brain tumor. DNA allelotyping showed retention of both parental chromosome 22 alleles in the RTK and loss of the maternal allele in the PNET. Evaluation of additional RTKs and brain tumors occurring in the same patient may provide insight into the origins and relationships of these enigmatic tumors.

ISSN:1045-2257    

DOI:10.1002/gcc.2870110303

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

年代:1994

数据来源: WILEY

摘要:

AbstractDue 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 los

ISSN:1045-2257    

DOI:10.1002/gcc.2870110304

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

年代:1994

数据来源: WILEY

摘要:

AbstractTwenty prostate tumor specimens, obtained from radical prostatectomies, and two lymph node metastases were examined by classical and molecular cytogenetic methods. A sample from each tumor was analyzed histologically and used for touch preparations. Adjacent samples were used for preparation of single‐cell suspensions before cell culture (DirFISH) and for establishing cell cultures, which were subsequently harvested for classical G‐banding analysis. Fluorescence in situ hybridization (FISH) was performed on touch preparations, DirFISH, and cells obtained from tissue culture. Biotinylated pericentromeric probes for chromosomes 7 and 17, in addition to a digoxigenin‐labeled X‐chromosome probe, were used in a dual‐color FISH assay. The results indicated that, in uncultured tumor cells, chromosome 17 was lost in 55% of specimens, chromosome 7 was gained in 16% of specimens, and 9% of specimens showed large tetraploid populations. After cell culture, 23% of specimens showed loss of chromosome 17, no specimens showed gain of chromosome 7, and no tetraploid populations were present. This study suggests that loss of chromosome 17 may play an important role in the development of prostate cancer, and that genetic changes observed after selection in vitro may not represent those in the origi

ISSN:1045-2257    

DOI:10.1002/gcc.2870110305

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

年代:1994

数据来源: WILEY

摘要:

AbstractTissue and tumor specific length variation of telomere (TTAGGG)nrepeats was studied in DNAs from various normal and malignant tissues. DNA was isolated from bone marrow and blood cells, malignant tissues, and established tumor cell lines. Nonisotopic Southern hybridization revealed a reduction of telomere repeat arrays in 14 of the 35 tumors analyzed. However, other cases (60%) showed no reduction, or even an increase, in telomeric length. Our finding of elongated telomere stretches in several tumors of different origin compared with normal tissue is in contrast to previous reports describing a general shortening of terminal repeat length in colorectal cancer and neuroblastoma. We tentatively conclude that there is no general tendency to telomere reduction in malignant tissues.

ISSN:1045-2257    

DOI:10.1002/gcc.2870110306

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

年代:1994

数据来源: WILEY

摘要:

AbstractA detailed cytogenetic analysis of 63 non‐small cell lung carcinomas (NSCLCs) was carried out for identification of recurrent chromosomal alterations. Most specimens displayed very complex karyotypes with multiple numerical and structural changes (median number, 31). Losses of chromosomes 9 (65% of cases) and 13 (71%) were the most frequent numerical changes. Loss of the Y was often observed in tumors from males. Gain of chromosome 7 was also frequent (41%). Chromosome arms 1p, 1, 3p, 3q, 6q, 7q, 8q, 9p, 11q, 17p, and 19q were particularly prone to rearrangement. The chromosome arm most often contributing to losses was 9p (79%). Other arms that were frequently lost included 3p, 6q, 8p, 9q, 13q, 17p, 18q, 19p, 21q, 22q, and the short arm of each acrocentric chromosome. The percentage of cases with loss of 3p was significantly higher in squamous cell carcinomas (94%) than in adenocarcinomas (60%). There was also a statistically significant increase in the proportion of cases with gains of 1q, 7p, and 11q in adenocarcinomas compared to squamous cell carcinomas. Several recurrent isochromosomes and unbalanced exchanges were found. Among these was i(5p), which was observed in nine tumors, eight of which displayed adenomatous features. An i(8q) was identified in six cases, including five adenocarcinomas. Double minutes and/or homogeneously staining regions were seen in seven specimens. These data indicate that numerous chromosome alterations contribute to the pathogenesis of NSCLC and that, amid this widespread genomic disarray, recurrent abnormalities exist that could have biological and clinical implication

ISSN:1045-2257    

DOI:10.1002/gcc.2870110307

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

年代:1994

数据来源: WILEY

摘要:

AbstractLoss of heterozygosity (LOH) from the short arm of chromosome 8 is frequent in a variety of malignancies, suggesting the presence of a tumor suppressor gene in this region. Previous studies suggested that this deletion may correlate with higher clinicopathologic stages in colorectal cancer, but others did not support this finding; in part, this difficulty is due to the low heterozygosity of the RFLP markers that were used. Here we report on a preliminary investigation in which we used highly informative microsatellite markers to determine whether deletions of 8p are correlated with poor prognostic features. Paraffin‐embedded tumor tissue from 15 patients was analyzed with a panel of three microsatellite markers that are known to be sites of frequent LOH. Fourteen of the 15 cases were informative with at least one marker, and 7 showed LOH. Analysis of clinical features showed that there was no relation of 8p LOH with patient age or tumor stage, grade, location, or pattern of growth. However, a statistically significant correlation was seen between LOH and lymphatic, vascular, or perineural microinvasion (Fisher exact test,P= 0.01). This histologic feature is known to be a stage‐independent indicator of prognosis. Our data suggest that 8p LOH may be associated with poor outcome and demonstrate the utility of these microsatellite markers for its detect

ISSN:1045-2257    

DOI:10.1002/gcc.2870110308

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

年代:1994

数据来源: WILEY

摘要:

AbstractShort‐term cultures of three hepatoblastomas were analyzed cytogenetically. Trisomy 2, trisomy 20, and a deletion of 17p were found as the sole abnormalities, yielding the karyotypes 47,XY, + 2; 47,XX, + 20; and 46,XX,del(17)(p12)/46,XX. This is the first reported case of deletion of 17p as the sole chromosomal abnormality in a hepatoblastoma and the first reported case of trisomy 20 without double minute chromosomes as a sole chromosomal abnormality in hepatoblastom

ISSN:1045-2257    

DOI:10.1002/gcc.2870110309

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

年代:1994

数据来源: WILEY

ISSN:1045-2257    

DOI:10.1002/gcc.2870110301

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

年代:1994

数据来源: WILEY