摘要:

AbstractThe somatic mutation theory of tumorigenesis states that mutations are necessary for tumor development. On the other hand, acquired, clonal chromosomal alterations are occasionally detected in otherwise normal, nonneoplastic cells—for example, loss of sex chromosomes occurs in bone marrow cells and lymphocytes in elderly individuals—and it is therefore evident that not all mutations are by themselves sufficient for neoplasia to occur. Thus, the finding of an acquired, clonal chromosomal abnormality does not constitute proof that a lesion is neoplastic. Trisomy 7 has, as the sole clonal chromosomal aberration, been reported in a wide variety of epithelial tumor types but also in some mesenchymal and neurogenic neoplasms. It has been suggested to be a primary, i.e., tumor‐initiating, abnormality in tumors of the bladder, brain, colon, kidney, lung, ovary, prostate, and thyroid. But data from cytogenetic studies of solid tumors, macroscopically normal tissue in the proximity of solid tumors, and nonneoplastic lesions now question the importance of a solitary +7 as a neoplasia‐associated change. Most solid tumors in which trisomy 7 has been found as the sole change in one clone have also displayed other, cytogenetically unrelated, clones with complex karyotypic abnormalities. Such karyotypic differences among coexisting clones could indicate that the neoplasm is polyclonal, that the cytogenetically disparate clones have emerged during tumor progression from one original clone carrying submicroscopic genomic changes only, or that the clone with +7 does not represent the tumor parenchyma. The latter interpretation is supported by the finding of cells with trisomy 7 in macroscopically normal tissue outside tumors of the brain, kidney, and lung. A seemingly decisive argument against the belief that the finding of an acquired, clonal +7 proves that a neoplasm exists is the detection of clones with an extra copy of chromosome 7 in several nonneoplastic lesions and tissues, such as atherosclerotic plaques, chorionic villi, chronic pyelonephritis, Dupuytren's contracture, focal steatosis of the liver, Peyronie's disease, and rheumatoid synovitis. That the abnormality arises in vivo has been shown by in situ hybridization with chromosome 7 specific probes; +7 is no in vitro artifact. It is unknown in which cell type the trisomy occurs; some data from colon adenomas favor epithelial cells, whereas data from kidney tumors and colon carcinomas suggest that the +7 arises in cells of the immune system. This question may possibly be resolved by obtaining a pure cell line with trisomy 7 cells only, to be characterized further by immunologic and morphologic methods. Another line of investigation might be to search for clonal chromosomal abnormalities in nonneoplastic tissues in other species. Finally, it remains to be elucidated whether +7 is a neutral genome mutation or whether it confers a selective advantage upon the cell. © 1993 Wiley

ISSN:1045-2257    

DOI:10.1002/gcc.2870060402

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

年代:1993

数据来源: WILEY

摘要:

AbstractChromosome studies were performed after short‐term in vitro culture of 39 samples from neurinomas and two samples from malignant schwannomas. Clonal abnormalities involving chromosome 22 were observed in 23 cases, as the sole chromosomal deviation in 12 of them. In 11 samples, other clonal numerical and/or structural aberrations were detected in addition to loss of chromosome 22, either in the same cells or in cells other than those having monosomy 22. Within the group of neurinomas with no involvement of chromosome 22, there were again two cytogenetically distinctive subgroups: one with an abnormal karyotype, and the second with a normal chromosome complement. Our findings confirm that monosomy 22 is a characteristic feature of this type of neoplasm, but also suggest the existence of different cytogenetic subgroups of neurinomas. © 1993 Wiley‐Liss,

ISSN:1045-2257    

DOI:10.1002/gcc.2870060403

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

年代:1993

数据来源: WILEY

摘要:

AbstractFive tenosynovial giant cell tumors—4 pigmented villonodular synovitis (PVNS) and 1 nodular tenosynovitis (NTS)—were investigated cytogenetically. Clonal chromosome aberrations were detected in 3 of them. One PVNS had t(7;16)(q22;q24) as the sole anomaly, whereas 1 PVNS and the NTS displayed aberrations suggesting clonal evolution: t(1;19)(p11;p12)/t(1;19), + 12 and ins(5;1)(q31;p13p34)/ins(5;1),t(2;4)(p23;q21), respectively. Including our 3 cases, a total of 6 tenosynovial giant cell tumors with karyotypic changes have been reported. Apart from 2 PVNS with trisomies 5 and 7, and 2 NTS with rearrangement of chromosome band 1p13, no recurrent chromosome change has been detected. Although the detection of clonal, acquired chromosome abnormalities has formerly generally been accepted as sufficient to conclude that a lesion is neoplastic, the interpretation of the pathogenetic significance of the karyotypic aberrations in synovial tumors is obscured by the fact that we have also detected comparable aberrations in obviously nonneoplastic synovial tissue. One of 2 lesions from patients with hemorrhagic synovitis carried a clonal del(13)(q12q21), and 2 of 4 synovectomy samples from patients with rheumatoid arthritis displayed –Y and –Y together with +7. The available cytogenetic data therefore cannot be used to resolve the controversy as to whether tenosynovial giant cell tumors are truly neoplastic or only reactive, inflammatory proliferations. © 1993 Wiley

ISSN:1045-2257    

DOI:10.1002/gcc.2870060404

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

年代:1993

数据来源: WILEY

摘要:

AbstractA chromosome 12‐derived marker was seen in each of 3 testicular germ cell tumors that lacked the i(12p). An interesting feature of 2 of the markers was that the major part, including the centromere, of an acrocentric (a #13 and #14, respectively) was translocated onto 12p, resulting in a dicentric. In the third tumor, 13q (translocated onto 12q) was again probably involved in the rearrangement. The findings support the view that the amplification of genes on 12p represents a significant step in the development of germ cell tumors. © 1993 Wiley‐Liss,

ISSN:1045-2257    

DOI:10.1002/gcc.2870060405

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

年代:1993

数据来源: WILEY

摘要:

AbstractDNA markers that map within the karyotypically defined band q13 on human chromosome 11 are amplified in a subset of mammary and squamous cell carcinomas. It is assumed that the amplified DNA includes a critical gene (or genes) whose overexpression provides a selective force in the development of the tumor. To help identify such genes, we have begun to construct a physical map of CpG islands in the region, making use of a squamous cell carcinoma cell line (UMSCC2) in which the 11q13 region is amplified 11‐fold. We previously described the proximal end of this amplicon and the order of markers extending ∼800 kb centromeric of theFGF3locus (formerlyINT2). We now report the use of chromosome jumping techniques to define additional CpG islands that lie distal toFGF3. These map within the amplified region in UMSCC2 cells and the most telomeric corresponds to theEMS1gene. The data imply that the amplified DNA in UMSCC2 cells extends for over 1,500 kb and includes at least 7 potential genes.EMS1andCCND1(formerlyPRAD1), the best candidates for the key gene on the 11q13 amplicon, are ≥800 kb apart. © 1993 Wiley‐L

ISSN:1045-2257    

DOI:10.1002/gcc.2870060406

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

年代:1993

数据来源: WILEY

摘要:

AbstractCytogenetic analysis of primary cell cultures and/or passages 1–3 of synovial tissue from seven patients with rheumatoid arthritis was performed. As the only recurrent chromosome aberration, trisomy 7 was found in six of seven cultures. In four cultures, trisomy 7 occurred as a clonal change in up to 20% of the analyzed cells, with an increase of the proportion of cells with +7 with the duration of the in vitro culture. Apart from this recurrent change, a variety of partly clonal, partly nonclonal numerical and structural chromosome aberrations were observed in all cases. These findings support the view that clonal chromosome aberrations may play a role in the pathogenesis of invasive growth of the synovial tissue in rheumatoid arthritis although the localized synovial hyperproliferation is not a true neoplastic process. © 1993 Wiley‐Liss,

ISSN:1045-2257    

DOI:10.1002/gcc.2870060407

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

年代:1993

数据来源: WILEY

摘要:

AbstractNeurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by development of bilateral acoustic neurinomas and increased incidence of meningiomas. Frequent losses of 1 allele of chromosome 22 in neurinomas and meningiomas has indicated that the gene responsible for NF2 functions as a tumor suppressor. Although theNF2gene has been mapped within a 13 cM region between D22S1 and D22S28 by linkage analysis, its location with respect to D22S15 is uncertain. We previously reported an NF2 patient with a constitutional balanced translocation t(4;22) (q12;q12.2); theNF2gene is probably disrupted at the breakpoint. To define the location of this breakpoint on chromosome 22, we performed fluorescence in situ hybridization (FISH) with DNA markers in theNF2region and determined the physical order of 5 loci: D22S1‐NF2‐LIF‐D22S15‐D22S32. © 1993 Wiley

ISSN:1045-2257    

DOI:10.1002/gcc.2870060408

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

年代:1993

数据来源: WILEY

摘要:

AbstractFibroblast contamination of epithelial tumor cell cultures is of great concern when examining tumor cells in vitro for specific biochemical and cytogenetic changes. The observations of normal karyotypes in thyroid tumor cell cultures have raised the concern of whether residual tissue fibroblasts might obscure the cytogenetic analysis of transformed epithelial cells. We have characterized early passaged thyroid tumor cells to examine the proportions of epithelial and fibroblastic cell types. Cells were analyzed by immunocytology using antibodies recognizing the thyroid prohormone thyroglobulin, epithelial cytokeratins, and vimentin, a mesenchyme marker. Tumors consisted of one follicular adenoma and five papillary carcinomas. When examined by day 15 in culture, all cells contained filaments composed of vimentin, which most likely represents an adaptation to culture conditions. Double immunofluorescence staining for thyroglobulin and cytokeratin revealed the presence of not only epithelial but also spindle‐like fibroblastoid cells possessing thyroid epithelial cell markers. The results suggest that in thyroid tumor cultures there is a unique cell type intermediate between epithelial and mesenchyme phenotypes that must be considered when performing cytogenetic analysis. © 1993 Wiley‐Liss,

ISSN:1045-2257    

DOI:10.1002/gcc.2870060409

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

年代:1993

数据来源: WILEY

摘要:

AbstractCytogenetic analysis of a thymoma showed the presence of a ring chromosome 6 as the sole chromosome abnormality. © 1993 Wiley‐Liss, I

ISSN:1045-2257    

DOI:10.1002/gcc.2870060410

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

年代:1993

数据来源: WILEY

摘要:

AbstractTheNME1gene, localized to human chromosome 17 at q22, shows reduced expression in tumors of high metastatic potential. A homologous gene,NME2, with similar reduced expression in breast carcinoma, has recently been reported. We have isolated and characterized five yeast artificial chromosome (YAC) clones and three cosmid clones that contain both genes, demonstrating that theNME2gene is also located on chromosome 17 and is separated by not more than 18 kb from theNME1gene. The two putative tumor suppressor genes, encoding the two polypeptide chains of nucleoside diphosphate (NDP) kinase, are thus quite close to each other on chromosome 17, indicating that they may well have arisen by a tandem duplication. Both genes now appear to be excluded as candidates for the early‐onset breast cancer (BRCA1) locus. © 1993 Wiley‐Liss,

ISSN:1045-2257    

DOI:10.1002/gcc.2870060411

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

年代:1993

数据来源: WILEY