摘要:

AbstractColorectal carcinogenesis is associated with the accumulation of genetic changes involving both dominant oncogenes and tumor suppressor genes. Although at least four different genes have been implicated in the process, the detection of allele loss from other regions of the genome suggests the involvement of additional genes. The short arm of chromosome 8 is one of these regions; loss of heterozygosity occurs at rates ranging from 30 to 50%. To define the region of common deletion containing the putative tumor suppressor gene, we analyzed a series of 87 carcinomas for allele loss in different regions of the short arm of chromosome 8 by using Southern blot analysis and a panel of polymorphic probes. We found allele loss in 33% of our cases, which involves two separate regions, one in the p‐terminal region of the chromosome, 8p23.1 ‐pter, where 45% of informative cases demonstrated loss, and the other in the mid‐p region, at 8p21, where 31% of cases showed allele loss. No tumors showed loss of heterozygosity for both regions. These findings suggest the presence of two discrete genes related to colorectal carcinogenesis on the short arm of chromosome 8. Genes Chrom Cancer 10:1–6 (1994). © 1994 Wiley

ISSN:1045-2257    

DOI:10.1002/gcc.2870100102

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

年代:1994

数据来源: WILEY

摘要:

AbstractTo isolate a putative tumor suppressor gene(s), we have constructed a physical map and a detailed deletion map of chromosome region 8p21.3‐p22, where loss of heterozygosity (LOH) has been frequently seen in human hepatocellular carcinomas (HCC), colorectal cancers (CRC), and non‐small cell lung cancers (NSCLC). The smallest commonly deleted region at 8p21.3‐p22 in HCC and CRC was between the loci defined by CI8‐245 and CI8‐2644; in NSCLC, a region between CI8‐1051 and CI8‐2644 was commonly deleted. A contiguous physical map of 12 cosmid markers in the 8p21.3‐p22 region was constructed by means of multi‐color fluorescence in situ hybridization (FISH) and pulsed‐field gel electrophoresis (PFGE). On the basis of this physical map, which spans roughly 3.1 Mb, the estimated sizes of the commonly deleted regions were at most 1.2 Mb in HCC and CRC and 0.6 Mb in NSCLC. As four of the 12 physically ordered markers are located within the 0.6 Mb region commonly deleted in all three tumor types, nearly one fourth to one fifth of the target region has already been covered with cosmid inserts. Genes Chrom Cancer 10:7–14 (1994).

ISSN:1045-2257    

DOI:10.1002/gcc.2870100103

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

年代:1994

数据来源: WILEY

摘要:

AbstractVariants of the t(15;17)(q22;q12‐q21) chromosomal rearrangement associated with acute promyelocytic leukemia (APL) have been previously described and they frequently involve either chromosome 15 and/or 17. Previously we reported a rare variant t(11;17). We now describe two patients with myelodysplastic syndrome (MDS) that transformed to APL‐like leukemia. Both had trisomy 11 at the diagnosis of APL‐like leukemia. Following treatment for APL, patient I reverted to MDS and showed a normal karyotype. When leukemia recurred, his bone marrow karyotype was 47,XY,t(4;11), +11,der(22)t(1;22). Both patients were treated with all‐trans retinoic acid (ATRA) for APL for 5 weeks, but failed to respond. The karyotype of patient I after ATRA treatment was 46,XY,t(4;11); the trisomy 11 had been lost and the bone marrow was replaced with immature myeloblasts without promyelocytes. In patient 2, the karyotype remained the same as at diagnosis, i.e., 47,X,‐Y,dir ins(4;7),del(5), +6,del(7), +8, +11,‐18. Molecular analysis by reverse transcriptase PCR analysis showed the presence of wild type retinoic acid receptor alpha (RARA) and the absence of thePML‐RARAchimeric gene associated with t(15;17). Additional analysis ofPLZF, a new zinc finger gene associated with t(11;17), also showed the absence of this hybrid gene. These data support the concept that APL is a heterogeneous disorder and that variants with chromosome 11 rearrangement exist that do not respond to ATRA. Genes Chrom Cancer 10:15–25 (1994). © 1994

ISSN:1045-2257    

DOI:10.1002/gcc.2870100104

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

年代:1994

数据来源: WILEY

摘要:

AbstractWe have characterised a region of deletion on the long arm of chromosome 6 (6q) in six cases of acute lymphoblastic leukaemia, by fluorescence in situ hybridisation, using a series of YAC clones which map to 6q. Conventional cytogenetic analysis of four of these cases had been interpreted as showing terminal deletions of 6q. We demonstrated by FISH that in all cases the deletions were interstitial. D6S246 (6q16.3) was the only marker which was missing in all six cases, indicating a common region of deletion between the markers M6PI at 6q14–15 andFYNat 6q21. Our results suggest the presence of a tumour suppressor gene within this interval. Genes Chrom Cancer 10:26–29 (1994). © 1994 Wiley‐Lis

ISSN:1045-2257    

DOI:10.1002/gcc.2870100105

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

年代:1994

数据来源: WILEY

摘要:

AbstractWe studied loss of heterozygosity (LOH) on chromosome arm Ip in 108 neuroblastomas using 14 polymorphic DNA markers. One‐hundred and four tumors with one or more informative loci; 21 (20%) of the 104 tumors showed LOH on Ip, and were classified into three groups on the basis of interstitial or terminal allelic loss, and presence or absence of LOH on Ip. Seven of the 21 tumors showed an interstitial deletion which encompassed a small region in Ip36 (group A), and the other 14 showed a terminal deletion which encompassed the region from I pter to Ip32 (group B). Eighty‐three tumors without LOH on I p were classified as group C. The group A patients were mostly less than 12 months of age (6/7), were frequently found by a mass screening program for infants (5/7), had a tumor of non‐adrenal origin, and rarely progressed to stage IV (1/7). Most group B patients were 12 months or older (11/14), were found clinically (11/14), had tumors of adrenal origin, and progressed to stage IV (10/14). Analysis of biologic characteristics in group C tumors suggested that they may comprise group A and B tumors. While all group A tumors were in the triploid range (3n) (4/4), most group B tumors were diploid (2n) or tetraploid (4n) (7/10).MYCNamplification was found in 8 group B tumors, but in none of group A tumors. Event‐free survivals of groups A, B, and C patients at 3 years were 86, 49, and 74%, respectively (P= 0.0287). These findings suggest that there may be two tumor suppressor genes on Ip which are closely associated with two biologically distinct subtypes of neuroblastoma. Genes Chrom Cancer 10:30–39 (1994). © 1994 Wiley

ISSN:1045-2257    

DOI:10.1002/gcc.2870100106

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

年代:1994

数据来源: WILEY

摘要:

AbstractMost Wilms' tumors contain several predominant cell types, of which a primitive blastemal population is often the most prominent. Other typical components include undifferentiated mesenchymal and epithelial cells, but it has not been demonstrated that these components are neoplastic. We used a combined cytogenetic and fluorescence in situ hybridization approach to determine the clonal relationship of different cell populations within six Wilms' tumors. Clonal numerical chromosome aberrations in three Wilms' tumors were found in blastemal cells, but not in mesenchymal cells. Loss of one WTl allele in two other tumors was detected in both blastemal and mesenchymal cells. Tetrasomy 18 in a sixth case was observed in mesenchymal and epithelial cells; blastemal cells could not be evaluated in this tumor. These findings demonstrate that mesenchymal and epithelial cells in some Wilms' tumors are neoplastic. Different histologic components in some Wilms' tumors derive from a single chromosomally aberrant ancestor which is most likely to be the primitive blastemal cell. Genes Chrom Cancer 10:40–48 (1994). © 1994 Wiley‐Liss,

ISSN:1045-2257    

DOI:10.1002/gcc.2870100107

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

年代:1994

数据来源: WILEY

摘要:

AbstractCytogenetic and molecular studies have demonstrated that involvement of 22q is a non‐random finding in malignant rhabdoid tumors (MRTs) of the brain. We present an MRT of the kidney with the karyotype 47,XY, +i(I)(q 10), der(8)t(8;22)(q12;q11.2),der(22)t(8;22)(q23 or q24.l;q11.2). This unbalanced reciprocal translocation was confirmed by fluorescence in situ hybridization (FISH) with chromosome‐specific paints for chromosomes 8 and 22. Molecular analysis demonstrated a partial deletion of 22q in the BCR region at q 11.2, strengthening the suspicion that this is a critical region for the initiation or progression of these highly malignant neoplasms. Establishing non‐random cytogenetic changes in MRTs arising from the kidney may be of value in distinguishing these rare, but often fatal tumors from other renal neoplasms that mimick them histologically. The similarity in cytogenetic and molecular abnormalities between renal and extra‐renal MRTs argues against the concept that extra‐renal MRTs are only representative of a rhabdoid phenotype, rather than being true rhabdoid tumors. Genes Chrom Cancer 10:49–54 (1994). © 1994 Wil

ISSN:1045-2257    

DOI:10.1002/gcc.2870100108

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe 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 theNFIlocus and lack of neurofibromin expression in these tumors suggest thatNFIgene mutations may contribute to the development of adrenal gland neoplasms in patients with NFI. Genes Chrom Cancer 10:55–58 (1994). © 1994 Wiley

ISSN:1045-2257    

DOI:10.1002/gcc.2870100109

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

年代:1994

数据来源: WILEY

摘要:

AbstractWe 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,

ISSN:1045-2257    

DOI:10.1002/gcc.2870100110

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

年代:1994

数据来源: WILEY

摘要:

AbstractA malignant fibrous histiocytoma (MFH) of bone arising in the fibula of a 21‐year‐old woman is described. Clinical, radiologic, and histologic findings demonstrated rapid tumor progression. Chromosomal analysis of the biopsy specimen showed great karyotypic heterogeneity, whereas the resection specimen four weeks later displayed a rather homogeneous karyotype. Both revealed a clonal t(14;22)(q11;p12). Several other clonal and non‐clonal chromosomal aberrations were observed. Some of these were previously described in giant cell tumor of bone (GCTB) and may correlate with aggressive behavior, e.g., aberrations involving 8p 11, 19q 13, and 20q 13. The change from karyotypic heterogeneity to relative homogeneity may be related to tumor progression. The chromosomal findings further suggest that the giant cell type of MFH of bone may be related to malignant GCTB. Genes Chrom Cancer 10:66–70 (1994). © 1994 Wiley

ISSN:1045-2257    

DOI:10.1002/gcc.2870100111

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

年代:1994

数据来源: WILEY