摘要:

AbstractUterine leiomyomata are thought to be monoclonal neoplasms. Accordingly, investigations of clonality with G6PD isoforms used as a marker for X chromosome inactivation have suggested independent origins for multiple tumors within individual uteri. However, results from a recent study assessing methylation differences between DNA of active and inactive X chromosomes have been interpreted to suggest that multiple tumors may arise from a common precursor. We have examined the clonality of 36 leiomyomata from 16 patients by analyzing X chromosome inactivation as indicated by the methylation status of the X‐linked androgen receptor gene. As shown by this assay, all informative leiomyomata were monoclonal in origin. In patients with multiple leiomyomata, a random distribution of inactivation between the X homologs was noted, consistent with an independent origin of each tumor. Cytogenetic analysis was also performed on short‐term cell cultures of 27 of the 36 tumors. In each of two tumors that had both cells with a clonal karyotypic abnormality and karyotypically normal cells, DNA prepared from short‐term cultures showed a monoclonal pattern of X inactivation identical to that of the leiomyoma from which they were derived. These data suggest that karyotypically normal cells present in short‐term cultures of uterine leiomyomata are part of the tumor clone, and that clonal expansion of tumor cells precedes the development of cytogenetic aber

ISSN:1045-2257    

DOI:10.1002/gcc.2870110102

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

年代:1994

数据来源: WILEY

摘要:

AbstractSchwannomas are benign tumors of cranial, spinal, and other nerve sheaths that develop sporadically or are inherited as part of neurofibromatosis type 2 (NF2). TheNF2gene (SCH) on chromosome 22 has recently been identified and shown to be inactivated by mutation and allele loss in some schwannomas. However, only limited regions in theSCHcoding region were examined for mutations. We have extended these studies by screening virtually all coding sequences of theSCHgene (95% coverage) and adjacent splice site sequences for the presence of mutations in 48 schwannomas. All tumors (34 vestibular schwannomas and 14 schwannomas of other locations) were additionally characterized for allele loss on chromosome 22. By PCR‐DGGE screening of the 16 known exons of theSCHgene, 22 mutations were found. Most of these give rise to a premature stop codon and are expected to result in the synthesis of a truncated gene product (schwannomin). Although there was no apparent hotspot for mutations, 16 of the 22 mutations occurred in the first eight exons or adjacent splice site sequences of theSCHgene. In several vestibular as well as other schwannomas loss of oneSCHallele and mutational inactivation of the second allele were identified in the same tumor. Our data indicate that theSCHgene is implicated in the development of schwannomas of all locations in the nervous syste

ISSN:1045-2257    

DOI:10.1002/gcc.2870110103

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

年代:1994

数据来源: WILEY

摘要:

AbstractCytogenetic analysis of mesothelioma cell lines and solid tumors has documented non‐random chromosomal abnormalities on the short arm of chromosome 3 from 3p 14 to 3p25. We therefore examined nine mesothelioma cell lines, their corresponding tumors, and 15 additional mesothelioma tumors for loss of heterozygosity on 3p from 3p 13 to 3p25.5 by polymerase chain reaction and restriction fragment length polymorphism analysis at 8 loci: D3S3, D3S30, D3S6, D3S2, D3S32, D3FI5S2,THRB, andVHLLoss of heterozygosity was documented by loss of one of two alleles in the tumor DNA whose corresponding normal DNA was heterozygous and was documented in four of nine mesothelioma cell lines and six of 15 mesothelioma tumors or a total of 42% of the mesotheliomas evaluated. This study suggests the involvement of a gene on the short arm of chromosome 3 in the development of mesothelioma

ISSN:1045-2257    

DOI:10.1002/gcc.2870110104

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

年代:1994

数据来源: WILEY

摘要:

AbstractDeletions of the long arm of chromosome 20 [del(20q)] are recurring abnormalities in patients with myeloid disorders. Although variable in size, these deletions are usually interstitial. With the object of defining a commonly deleted region for smaller 20q deletions, we used quantitative Southern blot analysis complemented by restriction fragment length polymorphism (RFLP) analysis to determine the copy number at 15 loci spanning 20q. The proximal breakpoints of three such deletions were found to separateHCKand the growth hormone releasing factor (GHRF) locus near the centromeric boundary of band 20q 11.2. The distal breakpoints were localized to the vicinity of the D20S22 locus in band q13.1.A candidate tumor suppressor gene,RBL2, and theSRConcogene were both located within the commonly deleted region. Six loci in terminal region q13.2‐q13.3 were conserved on these del(20q) chromosomes, thereby confirming that the deletions were interstitial. Molecular heterogeneity at one and possibly both deletion breakpoints rules out the pathological involvement of loci at these sites. Instead, loss of a tumor suppressor locus from within the commonly deleted region may contribute to deregulated hemopoiesi

ISSN:1045-2257    

DOI:10.1002/gcc.2870110105

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

年代:1994

数据来源: WILEY

摘要:

AbstractClonal chromosomal abnormalities were characterized in nine cell lines established from squamous cell carcinomas of the head and neck. Aneuploidy was a common feature; one cell line was near‐diploid, three were near‐triploid, four were near‐tetraploid, and one cell line showed extensive variation in chromosome numbers. Consistent numerical abnormalities included loss of the sex chromosomes in six cell lines, losses of chromosomes 2 and 21 in six and five cell lines, respectively, and gain of chromosome 20 in five cell lines. Recurrent structural rearrangements included del(10)(q22‐q26) (seven cell lines), i(5)(p10) (six cell lines), i(8)(q10) (six cell lines), add(19)(q13) (six cell lines), del(4)(q21‐q31.3) (five cell lines), i(3)(q10) (four cell lines), del(12)(p11.1‐p12) (four cell lines), and add (18)(q21‐q23) (four cell lines). Other changes were noted in lower frequencies. Loss of specific regions on chromosomes 2, 3p, 4q, 5q, 8p, 10q, 12p, 18q, 19q, and 21 suggests that they may represent sites of putative tumor suppressor genes, loss of which may play a role in the pathogenesis of squamous cell carcinomas of the head and neck. Alternatively, gain of chromosomal region 3q, 5p, and 8q due to isochromosome formation suggests that more than one mechanism is involved in malignant transformation. Cytogenetic evidence of gene amplification was found in two cell lines; as an hsr(11)(q 13) in one and as dmins in the other. The clonal karyotypes of four cell lines were compared with those of their respective primary tumors. In all cell lines, clonal evolution had occurred, with loss of some rearrangements present in the primary tumors or the gain of additional

ISSN:1045-2257    

DOI:10.1002/gcc.2870110106

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

年代:1994

数据来源: WILEY

摘要:

AbstractIn contrast to the cytogenetically well characterized testicular germ cell tumors (GCT) in adults, reports on cytogenetic studies in pediatric GCT are scarce. The presence of an i(12p) and numerical abnormalities involving chromosome 12 are the most frequent cytogenetic changes in GCT of adults. We have performed in situ hybridization (ISH) studies on paraffin sections and on isolated nuclei of 13 pediatric GCT with particular emphasis on those chromosome abnormalities that are common in adult GCT. These include numerical and structural abnormalities of chromosomes 1 and 12 as well as numerical deviations of chromosomes 8, 10, X, and Y. The histological subsets of the tumors investigated included two dysgerminomas (DGE), one seminoma (SE), two embryonal carcinomas (EC), four mixed and two pure yolk sac tumors (YST), and one undifferentiated (IT) and one differentiated teratoma (TD). Similar to the GCT in adults, additional copies of chromosome 12 were the most frequently observed numerical abnormalities. In contrast to the findings in adult GCT, changes in the size of the pericentromeric hybridization signals of chromosome 12, suggesting the presence of i(12p) chromosomes, were found in only two cases. No chromosome abnormalities were found in the pure TD or in the TD cells of mixed tumors containing a YST component. In the YST portion, however, Ip deletions and/or numerical chromosome changes were present. Surprisingly, deletions of the short arm of chromosome I, del(I)(p36.3), were frequent in pediatric GCT and were the sole abnormality detected in two cases. The Ip36 deletions were present in all stage‐IV EC and YST investigated and were absent in the relatively benign TD and in one YST stage‐I. Therefore, Ip36 deletions may have value as a prognostic marker in pediatric

ISSN:1045-2257    

DOI:10.1002/gcc.2870110107

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

年代:1994

数据来源: WILEY

摘要:

AbstractPCR analysis of DNA from a selected panel of human‐rodent somatic cell hybrids and fluorescent in situ hybridization (FISH) analysis allowed us to localize the humanELEIgene. This previously uncharacterized gene is fused with the tyrosine kinase (tk) domain of theRETproto‐oncogene to generate the oncogenic sequenceRET/PTC3, thus providing a third example ofREToncogenic activation in papillary thyroid carcinomas.ELEIwas localized to band 10q11.2, the subband whereRETalso maps, at a minimum distance of more than 500 kb from the proto‐oncogene. The fusion event corresponding to the rearrangement reciprocal to that leading to the formation ofRET/PTC3was also identified and characterized. The karyotype of twoRET/PTC3positive tumors did not show any evidence of chromosome 10 abnormalities. The data indicate that a cytogenetically undetectable paracentric inversion within 10q11.2 generatesRET

ISSN:1045-2257    

DOI:10.1002/gcc.2870110108

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

年代:1994

数据来源: WILEY

摘要:

AbstractLinkage studies have indicated that a gene on chromosome arm 17q, designatedBRCAI, confers susceptibility to familial breast and ovarian cancer. To investigate the possible involvement of theBRCAIgene in sporadic breast cancer we have analysed loss of heterozygosity (LOH) in a panel of 100 sporadic primary breast tumours using 10 PCR‐based polymorphic markers from 17q12–21. Allele losses were detected in 40 of 100 tumours informative for at least one of the markers analysed. Of these 40 deleted tumours, 27 showed partial or interstitial loss on 17q. The pattern of LOH in the tumours with partial or interstitial LOH revealed three putative distinct deleted regions on 17q12–21. The first lies on the proximal long arm between D17S250 andTHRAI; the second one lies between D17S776 and D17S579, the region containing theBRCAIgene; and the third is telomeric to D17S733. The most frequently deleted region overlaps with the minimal region containing theBRCAIgene, suggesting that this gene might also be associated with the development or progression of a proportion of sporadic breast tu

ISSN:1045-2257    

DOI:10.1002/gcc.2870110109

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

年代:1994

数据来源: WILEY

摘要:

AbstractWe report the amplification and overexpression of theIGFIR(insulin‐like growth factor I receptor) gene in primary breast cancers with an amplification of band 15q26. The involvement ofIGFIR, which may vary in frequency from 2‐3% in unselected tumor series to more than 10% in breast cancers with hsr, may represent an important event in tumor progress

ISSN:1045-2257    

DOI:10.1002/gcc.2870110110

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe Heregulin (HGL) gene, encoding a ligand for a member of theERBBreceptor family, is located at 8p 12‐p22, in or close to a region frequently amplified in breast carcinoma. Amplification ofHGLwas detected in three of 83 (3.6%) cases of breast tumors. No overexpression of the gene was observed in the amplified tumors. This and the low incidence of amplification suggest thatHGLis not the key gene of the 8p 12 amplification but may be used as a marker of large amplification unit

ISSN:1045-2257    

DOI:10.1002/gcc.2870110111

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

年代:1994

数据来源: WILEY