摘要:

AbstractTranslocations and deletions involving chromosomal band 22q 11 are common genetic aberrations in malignant rhabdoid tumors. Previous molecular analyses of a t(11; 22) in the malignant rhabdoid tumor cell line TM87‐16 localized the breakpoint distal toBCRon 22q 11. In the present report, we have further refined the map position of this breakpoint betweenCRYBB2and D22S258. Moreover, the D22S258,CRYBA4, D22S300, D22SI, and D22S310 loci, which lie between CRYBB2 and D22S42, were found to be deleted, presumably as a result of the translocation event. The identification of this deletion of at least 2 Mb on the long arm of chromosome 22 should be helpful for mapping the gene(s) in the region involved in the development of malignant rhabdoid tumors as well as providing insights into the mechanisms of chromosomal translocation in human solid tumor

ISSN:1045-2257    

DOI:10.1002/gcc.2870130302

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

年代:1995

数据来源: WILEY

摘要:

AbstractPheochromocytomas occur sporadically and are associated with several dominantly inherited cancer syndromes, including von Hippel‐Lindau (VHL) disease. We examined 14 pheochromocytomas (four from VHL patients, nine from sporadic patients, and one from a patient with familial pheochromocytoma) for loss of heterozygosity on chromosome arm 3p by using the polymerase chain reaction and restriction fragment length polymorphisms at eight loci. Loss of heterozygosity was detected in 8 of 14 pheochromocytomas examined: in three of the four VHL‐associated tumors, in four of the nine sporadic tumors, and in the familial pheochromocytoma‐associated tumor. Deletion of the inherited wild‐typeVHLallele was demonstrated in both informative VHL‐associated pheochromocytomas, demonstrating involvement ofVHLin pheochromocytoma development. However, becauseVHLmutations have not been detected in sporadic pheochromocytomas,VHLand/or another chromosome arm 3p gene may be involved in the etiology of these tumors. © 1995 Wiley

ISSN:1045-2257    

DOI:10.1002/gcc.2870130303

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

年代:1995

数据来源: WILEY

摘要:

AbstractChromosome studies performed on 3I papillary thyroid carcinomas (PTCs) revealed clonal numerical and structural abnormalities in I2 tumors. The numerical clonal aberrations found were trisomy 2, trisomy 7, and loss of the Y chromosome. A nonrandom telomeric association, tas( I5; I6)(p I3; p I3), was observed in one carcinoma. Structural alterations with a breakpoint at I0q II.2 were detected in two tumors. Other chromosomes involved in rearrangements were chromosomes I, 2, 3, 5, 7, 9, II, 12, and 14. The observation of clonal changes of chromosome 2 [i(2)(qI0) and trisomy 2] in two tumors, which were both histologically classified as tall‐cell PTC variants, suggests that gain of 2q may be important in the development of this morphological variant. © 1995 Wiley‐Liss,

ISSN:1045-2257    

DOI:10.1002/gcc.2870130304

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

年代:1995

数据来源: WILEY

摘要:

AbstractTo investigate cumulative genetic changes during development and progression of hepatocellular carcinoma (HCC), we examined DNAs isolated from I04 tumors for loss of heterozygosity (LOH) at I 3 loci on six chromosomal arms and for an increase of copy number (“multiplication”) of alleles on 8q, using polymorphic microsatellite markers. A comparison of genetic features with clinicopathological stages of these tumors revealed that LOH on I p had occurred in tumors at an early stage or with a well‐differentiated histological phenotype (8/26 31 %) as well as in tumors at more advanced stages. Genetic alterations on chromosome arms 4q. 8p, 8q, I 3q, I6q, and I7p were more often observed in tumors of more advanced stages and poorer differentiation grades. When size was the criterion for comparison, LOH on I p was observed frequently even in tumors smaller than 2 cm (6/16; 38%), whereas allelic losses on 16q were detected frequently only in larger tumors. These results suggest that the putative tumor suppressor gene(s) assumed to be located on I p may be involved in an early step of carcinogenesis in liver tissue and that the other genetic alterations examined here may play important roles in progression of HCC. © 1995 Wiley‐L

ISSN:1045-2257    

DOI:10.1002/gcc.2870130305

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

年代:1995

数据来源: WILEY

摘要:

AbstractHuman prostate cancers frequently show loss of heterozygosity at loci on the short arm of chromosome 8. In order to take a step toward isolation of the putative tumor suppressor gene(s) on 8p via positional cloning, we performed high‐resolution deletion mapping in 46 prostate cancers (stage B, 20 cases; stage C, 8 cases; endocrine therapy‐resistant cancer death, 18 cases) using new 12 restriction fragment length polymorphism markers for this chromosomal region. Allelic losses were observed in 25 of the 44 cases (57%) that were informative with at least one locus. Detailed deletion mapping defined a 1.2 Mb commonly deleted region at 8p22‐p2 1.3 flanked by markers cMSR‐32 and C18‐ 105 1. A second region of common deletion was identified between C18‐1312 and C18‐494 at 8p21‐8p11.22, suggesting that at least two tumor suppressor genes associated with prostate cancer are present on chromosome arm 8p. Allelic losses on 8p were observed more frequently in the cancer death cases (14/17, 82%) than in early‐stage tumors (11/27, 40%;P<0.01, Fisher's exact test). In two out of 7 patients for whom DNA was available from metastatic cancers as well as from normal tissues and primary tumors, the primary cancer foci had no detectable abnormality of 8p, but the metastatic tumors showed loss of heterozygosity. These results suggest that inactivation of tumor suppressor genes on 8p plays an important role in the progression of prostate cancer. © 19

ISSN:1045-2257    

DOI:10.1002/gcc.2870130306

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

年代:1995

数据来源: WILEY

摘要:

AbstractIdentification of the genetic alterations that occur in tumors is an important approach to understanding tumorigenesis. We have used comparative genomic hybridization (CGH), a novel molecular cytogenetic method, to identify the gross DNA copy number changes that commonly occur in small cell lung cancer (SCLC). We analyzed ten SCLC tumors (seven primary tumors and three metastases) from eight patients. We found frequent increases in DNA copy number on chromosome arms Sp, 8q, 3q, and Xq and frequent decreases in copy number on chromosome arms 3p. 17p, Sq, 8p, 13q, and 4p. The increase in copy number at 8q24 (MYC) and decreases at 17p 13 (TP53), 13q 14 (RB), and 3p have previously been identified in SCLC with other methods. Many of the other regions in which we detected common copy number changes have not been reported to be regions of common alteration in SCLC tumors. Comparison of copy number changes between a primary tumor and a metastasis from the same patient showed that they were more closely related to each other than to any of the other tumors. The results of direct CGH analysis of SCLC tumors reported here confirm the existence of copy number changes that we identified previously by using cell lines. © 1995 Wiley‐Liss, I

ISSN:1045-2257    

DOI:10.1002/gcc.2870130307

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

年代:1995

数据来源: WILEY

摘要:

AbstractLoss of heterozygosity (LOH) from the short arm of chromosome 8 (8p) is common to many human carcinomas, including those of the colon and prostate. It localizes to two discrete regions, 8p21 and 8p22. This suggests the presence of at least two tumor suppressor genes (TSGs) on this chromosome arm. Human breast cancers show consistent 8p deletions in cytogenetic studies, chromosome 8 aneusomy and isochromosome 8q, indicating that the relevant gene(s) may play a role, but the results of molecular analyses of chromosome 8 in breast cancer have been variable. We present here data for 8p LOH in an unselected series of human breast cancers with the use of three CA‐repeat markers that showed high rates of LOH in other tumors. All cases were informative for at least one marker, and LOH was seen in 11 of 20 cases (55%). LOH was more frequent for the 8p22 markers D8S254 and D8S 133 than for NEFL in 8p21. Regional metastases of the tumors showed allele profiles identical to those of their primaries regardless of whether there was LOH or retention of alleles. One case of microsatellite instability (RER+) was seen. LOH did not correlate with receptor status, ploidy, percentage of cells in S phase, or tumor size: We observed LOH at equal rates in small (2 cm) tumors. The data suggest that LOH from 8p is frequent in human breast cancers and that loss of the putative 8p TSG may be an important event in early stage breast cancer. © 1995 Wiley‐Liss,

ISSN:1045-2257    

DOI:10.1002/gcc.2870130308

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

年代:1995

数据来源: WILEY

摘要:

AbstractFamilial adenomatous polyposis (FAP) is an inherited predisposition to colorectal cancer caused by germline mutations in the adenomatous polyposis coli (APC) gene located on chromosome segment 5q21‐q22. We detected a germline rearrangement of theAPCgene in a Dutch FAP family by screening genomic DNA samples with APC cDNA probes. Subsequent molecular and cytogenetic studies revealed a constitutional reciprocal translocation t(5; 10) (q22; q25) that resulted in the disruption of the APC gene. Southern blot and polymorphic marker analysis indicated that part of theAPCgene had been deleted. Analysis of theAPCprotein product indicated that the translocation breakpoint did not lead t o the formation of a detectable truncated APC protein but apparently resulted in a null allele. Evaluation of the clinical phenotypes in the patients suggested that they exhibited features of an unusual form of FAP characterized by a slightly delayed age of onset of colorectal cancer and a reduced number of colorectal polyps. The latter were mainly sessile and were located predominantly in the proximal colon. To our knowledge, this is the first description of FAP caused by a reciprocal translocation disrupting theAPCgene. © 1995 Wiley‐Liss,

ISSN:1045-2257    

DOI:10.1002/gcc.2870130309

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

年代:1995

数据来源: WILEY

摘要:

AbstractLoss of heterozygosity (LOH) was evaluated in 174 breast and ovarian tumors derived from 94 families with at least 3 first‐degree relatives affected with either of these cancers. By linkage analysis 26 families were identified as having a high posterior probability of being due toBRCAI(the breadovarian cancer susceptibility locus on 17q 12–21) with lod scores varying from 0.5 1 to 9.49. Tumor genotypes were determined at at least 2 constitutionally heterozygous markers flanking BRCA I in a total of 58 tumors from these families. These tumors were derived from 52 patients, theBRCAImutation carrier status of which was evidenced by DNA sequencing in 20, and inferred by reconstructing haplotypes in the remainder. LOH was detected in 50 (86%) tumors. and invariably involved the wild‐type allele. Where informative, this allele was of paternal origin in 33 cases and of maternal origin in I0 cases. These results strongly suggest that BRCA I is a tumor suppressor gene and that LOH is greatly favored to fully inactivate it. © 1995 Wiley‐L

ISSN:1045-2257    

DOI:10.1002/gcc.2870130310

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

年代:1995

数据来源: WILEY

摘要:

AbstractTheNF2gene is a putative tumor‐suppressor gene that, when it is altered in the germline, causes neurofibromatosis type 2, a tumor‐susceptibility disease that mainly predisposes to schwannomas and meningiomas. The recent isolation of theNF2gene on chromosome 22 allows the identification of somatic mutations in human tumors. We have searched for mutations of theNF2gene in 331 primary human tumors using a screening method based on denaturing gradient gel electrophoresis, which allows the detection of mutations in 95% of the coding sequence. Mutations were observed in 17 of 57 meningiomas and in 30 of 89 schwannomas. No mutations were observed for 17 ependymomas, 70 gliomas, 23 primary melanomas, 24 pheochromocytomas, 15 neuroblastomas, 6 medulloblastomas, 15 colon cancers, and 15 breast cancers. All meningiomas and one‐half of the schwannomas with identifiedNF2mutations demonstrated chromosome 22 allelic losses. We conclude that the involvement of theNF2gene in human tumorigenesis may be restricted to schwannomas and meningiomas, where it is frequently inactivated by a two‐hit process. © 1995 Wiley

ISSN:1045-2257    

DOI:10.1002/gcc.2870130311

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

年代:1995

数据来源: WILEY