摘要:

AbstractTwenty‐five radical prostatectomy specimens were screened for the presence of numerical chromosome changes within the adenocarcinoma as well as in 17 adjacent prostatic intraepithelial neoplasias (PIN) by means of interphase in situ hybridization (ISH) to routinely processed tissue sections. To this end a defined alfoid repetitive DNA probe set was used, specific for the centromeres of chromosomes 1, 7, 8, 10, 15, and Y. The cytogenetic information was correlated with histopathological and clinical features as well as with DNA ploidy. Numerical aberrations of at least one chromosome were shown in 13 of 25 cases (52%). Alterations of chromosome 8 and loss of the Y chromosome were the most frequent findings (both 20%), followed by loss of chromosomes 15 (16%) and 10 (12%). Gain of chromosome 7 was seen in 8% of cases. No aberrations of chromosomes 7, 8, 10, and 15 were found in the adjacent PIN lesions, whereas loss of the Y chromosome in both PIN and tumor occurred in two cases. Also, (low level) aneuploidy was observed in 76% of these PIN lesions. Ploidy of the carcinomas as assessed by ISH correlated well with ploidy measured by DNA flow cytometry (FCM;P<0.02). Due to the more specific correspondence between ISH and tumor pathology, pathologic grade correlated with ISH aneuploidy (P<0.05), whereas FCM ploidy did not. Furthermore, genetic heterogeneity within a tumor was seen, as judged by the focal appearance of chromosomal aberrations. Chromosomal alterations occurred in all grades and stages, although loss of chromosome 10, gain of chromosome 7, and aberrations of chromosome 8 tended to predominate in more advanced cancer

ISSN:1045-2257    

DOI:10.1002/gcc.2870120402

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

年代:1995

数据来源: WILEY

摘要:

AbstractWidespread mutations in simple tandemly repeated (STR) DNA sequences are frequently found in colorectal tumors from patients with hereditary non‐polyposis colorectal cancer (HNPCC) and less frequently in sporadic colorectal cancers. The aims of this study were to determine the type of DNA sequence most commonly affected by such mutations and to examine the point in the natural history of the tumor where replication errors (RERs) appear. An unselected series of colorectal tumors (49 adenomas and 108 carcinomas) was examined with 4 different STR markers: oneAluVpA polymorphism (MYCL1), one tetranucleotide repeat (D17S846), one dinucleotide repeat (D3S1029), and one polyA repeat (APΔ3Δ). All 3 positive adenomas and 18 of 20 positive carcinomas showed replication errors in theAluVpA sequence at theMYCL1locus, making this marker more than twice as sensitive as the best of the other 3 markers. Importantly, all positive adenomas showed small foci of carcinoma in situ. This suggests that replication errors manifest at the adenoma/carcinoma transition in sporadic colorectal tum

ISSN:1045-2257    

DOI:10.1002/gcc.2870120403

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

年代:1995

数据来源: WILEY

摘要:

AbstractA number of cytogenetic and molecular analyses have revealed very frequent and extensive losses of regions of chromosome 10 in human glioblastomas. Our recent studies have demonstrated that the transfer of a chromosome 10 into human glioblastoma cells resulted in suppression of their transformed and tumorigenic phenotype. To localize the suppressive region further, we isolated and characterized certain hybrid cells that had undergone chromosomal rearrangements to yield hybrid cells retaining only various regions of the inserted chromosome 10. One series of subclones showed the loss of the majority of the long arm of chromosome 10 (10q21‐10qter) and regained the ability to grow under anchorage‐independent conditions, but the cells still failed to exhibit significant tumorigenicity in nude mice. Another set of subclones exhibited major deletions of large segments of the long arm of chromosome 10 (10q21‐q23; 10q26‐qter), yet retained certain distal alleles associated with 10q24 to 10q26. These subclones were identical in their biological characteristics to the hybrids containing an intact chromosome 10, exhibiting no growth in soft agarose or in nude mice. These results implicate the presence of two independent phenotypically suppressive regions on chromosome 10 (10pter‐q11 and 10q24‐q26) that are involved in glioma

ISSN:1045-2257    

DOI:10.1002/gcc.2870120404

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

年代:1995

数据来源: WILEY

摘要:

AbstractGene amplification allows transformed cells to overexpress specific genes and gain a survival advantage. For this reason, cloning and characterization of amplified genes can improve our understanding of the biology of transformed cells. The techniques of in‐gel renaturation and chromosome microdissection can enrich for amplified DNA sequences, but both are labor intensive and have other drawbacks. We have developed an alternative strategy of enriching for amplified DNA sequences that involves two‐directional agarose gel electrophoresis of extrachromosomal circular DNA. Extrachromosomal circles can be detected with repetitive DNA probes and can be used to produce DNA probes suitable for fluorescence in situ hybridization for location of genomic origin. The ability to enrich for amplified DNA without specialized equipment or transformed cell metaphases should prove useful in the search for new genes which are important in tumor cell progress

ISSN:1045-2257    

DOI:10.1002/gcc.2870120405

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe DNA‐repeat [(CA)n] instability of colorectal cancer cells was studied relative to our previously defined classification based on chromosome alterations. Of the 23 tumors analyzed, 13 belonged to the “monosomic” type (MT) characterized by simultaneous loss of chromosome 18 and chromosome arm 17p, and many structural rearrangements, 7 to the “trisomic” type (TT) with many chromosome gains but few rearrangements, and 3 had a normal karyotype (NT). (CA)n repeat sequences were examined on chromosomes 2, 5, 11, 13, 18, and 20. We found sequence alterations in 12 tumors at 1 or several loci, 9 of which (1/13 MT, 5/7 TT, and 3/3 NT) exhibited a typical shift in allele size defined as microsatellite instability. Furthermore, a single alteration was observed for the MT tumor, whereas one NT tumor displayed instability on two and all the other tumors on three or more loci. These results suggest an inverse relationship between the occurrence of chromosome structural rearrangements and microsatellite instability, providing another argument for the subdivision of colorectal cancers into groups of distinct oncogenic

ISSN:1045-2257    

DOI:10.1002/gcc.2870120406

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

年代:1995

数据来源: WILEY

摘要:

AbstractAllelic mutation on chromosome 19 has previously been reported as a frequent genetic event in human glial tumors. In an effort to localize specific regions of importance on this chromosome better, 13 highly polymorphic genetic markers distributed along the length of chromosome 19 were used for evaluation of loss of heterozygosity (LOH) and microsatellite instability in a total of 100 brain tumors, including 75 astrocytomas (55 grade 4; 7 grade 3; 5 grade 2; 6 grade 1; and 2 other), 17 oligodendrogliomas (1 grade 4; 5 grade 3; 10 grade 2; and 1 grade 1), and 8 mixed oligoastrocytomas (MOA) (3 grade 4; 2 grade 3; and 3 grade 2). No microsatellite expansion was observed in these glial tumors for any of the chromosome 19 loci examined. LOH for loci on chromosome 19 was detected in 23/74 informative astrocytomas (31%), 11/17 oligodendrogliomas (65%), and 3/8 MOA (38%). Partial deletion of chromosome 19 occurred more frequently (31/37 cases) than did loss of one whole copy of the chromosome, and a morphology‐specific pattern of LOH was observed. In 12/14 (86%) instances of chromosome 19 deletion in oligodendrogliomas and MOA, the 19q arm showed LOH, whereas the 19p arm showed no loss for all informative loci. Conversely, in 17/23 (74%) instances of chromosome 19 deletion in astrocytomas, the 19p arm showed LOH, whereas the 19q arm showed no loss for one or more loci. Thus, loss of 19q and retention of 19p are strongly associated with oligodendroglioma and MOA, whereas loss of 19p and retention of distal 19q is associated with astrocytoma. These data indicate that two or more tumor suppressor genes may reside on chromosome 19, one on 19p important in the development of astrocytomas, and one on 19q important in oligodendrogliomas and MO

ISSN:1045-2257    

DOI:10.1002/gcc.2870120407

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

年代:1995

数据来源: WILEY

摘要:

AbstractThere are five reported cases of an atypical myeloproliferative disorder in which the leukemia cells have a consistent t(8;13)(p11;q12) translocation. We analyzed the breakpoint in metaphases from two of these patients by fluorescence in situ hybridization using a series of yeast artificial chromosomes (YACs) derived from the 13q12 region. We found that a YAC containing theFLT1andFLT3oncogenes was localized distal to the 13q12 breakpoint and was not rearranged. YAC 66, a YAC that lies immediately adjacent to the chromosome 13 centromere, was localized proximal to the 13q12 breakpoint and was not rearranged. A third YAC, which is located betweenFLT1and YAC 66, was unrearranged in normal metaphase chromosomes, but showed hybridization signals on both derivative chromosomes in both cases. Thus, the breakpoints in these two cases are localized to the same 1.5 Mbp region of 13q12. This may be the site of an unidentified gene involved in the pathogenesis of some types of leukemia.

ISSN:1045-2257    

DOI:10.1002/gcc.2870120408

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

年代:1995

数据来源: WILEY

摘要:

AbstractOral squamous cell carcinoma (OSCC) develops along a multistep genetic pathway including loss of tumor suppressor genes and alteration of oncogenes. We characterized seven OSCC cell lines by classical and molecular cytogenetic analysis and fresh tumor and adjacent oral mucosa corresponding to three of the cell lines by molecular cytogenetics. We observed homogeneously staining regions (hsrs) in four of the seven cell lines, at 11q13 in three and at 11q23 and in an unidentified marker chromosome in the fourth. Amplification of band 11q13 occurs in 30–60% of head and neck squamous cell carcinomas. To determine whetherINT2andHST1, both located in band 11q13, are amplified in the tissues and cell lines and to confirm the chromosomal location(s) of the amplification, we used dual‐color fluorescence in situ hybridization (FISH) with DNA probes for these genes and the chromosome 11 centromere. We report chromosomal localization ofINT2/HST1amplification in OSCC. Coamplification ofINT2andHST1was detected in the hsrs in cultured tumor cells from the four hsr‐containing tumors and in directly harvested tumor cells, which were available from only two of these tumors. Amplification was not present in tumors lacking hsrs or adjacent oral mucosa corresponding to any of the seven tumors. The observation of amplification in fresh tumor cells suggests that the amplification was present in the patients, may play a key role in the development and/or progression of OSCC, and is not due to karyotypic evolution in vitro. The absence of amplification in the adjacent mucosa suggests that 11q13 amplification is a relatively late event in OSCC tumorige

ISSN:1045-2257    

DOI:10.1002/gcc.2870120409

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

年代:1995

数据来源: WILEY

摘要:

AbstractChromosome arm 12q breakpoints in seven cell lines derived from primary pleomorphic salivary gland adenomas were mapped by FISH analysis relative to nine DNA probes. These probes all reside in a 2.8 Mb genomic DNA region of chromosome segment 12q13‐q15 and correspond to previously published sequence‐tagged sites (STS). Their relative positions were established on the basis of YAC cloning and long range physical and STS content mapping. The 12q breakpoints of five of the cell lines were found to be mapping within three different subregions of the 445 kb DNA interval that was recently defined as the uterine leiomyoma cluster region of chromosome 12 breakpoints (ULCR12) between STS RM33 and RM98. All seven breakpoints appeared to map within the 1.7 Mb DNA region between STS RM36 and RM103. Furthermore, the chromosome 12 breakpoints of three primary pleomorphic salivary gland adenomas were also found to be mapping between RM36 and RM103. Finally, FISH analysis of two lipoma cell lines with 12q13‐q15 aberrations pinpointed the breakpoints of these to relatively small and adjacent DNA segments which, as well as those of two primary lipomas, appeared to be located also between RM36 and RM103. We conclude from the observed clustering of the 12q breakpoints of the three distinct solid tumor types that the 1.7 Mb DNA region of the long arm of chromosome 12 between RM36 and RM103 is a multiple aberration region which we designat

ISSN:1045-2257    

DOI:10.1002/gcc.2870120410

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

年代:1995

数据来源: WILEY

摘要:

AbstractAlthough human breast tumorigenesis is associated with the accumulation of mutations both in oncogenes and in tumor suppressor genes, the identity of the genetic alterations that are critical in the early stages of the breast tumorigenic process remains obscure. A high frequency (27–41%) of loss of heterozygosity (LOH) occurrence has been shown at theMETlocus on chromosome band 7q31 and this specific alteration is associated with poorer survival. Here, we report that restriction fragment length polymorphism (RFLP) analysis on 221 informative (heterozygous) primary breast tumors and 57 informative relapses (13 local recurrences and 44 distant metastases) revealed a similar frequency of 7q31 LOH as tumors progress from primary cancer to relapse, in marked contrast to other changes such as 11p15.5 LOH. This finding suggests that inactivation of a putative tumor suppressor gene located in 7q31 is a very early event in breast tumorigenesis. Our results also show that metastatic potential is an induced phenomenon that occurs at a relatively early stage, rather than a marker of tumor progressio

ISSN:1045-2257    

DOI:10.1002/gcc.2870120411

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

年代:1995

数据来源: WILEY