ISSN:1045-2257    

DOI:10.1002/gcc.2870050302

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

年代:1992

数据来源: WILEY

摘要:

AbstractWhether cancer cytogenetics can be reduced to the molecular genetics of cancer cells is a question that must be addressed in three domains, focusing on its ontological, methodological, and epistemological dimensions. The possibility ofontological reductionhinges on whether chromosomes have other important constituents than molecules. Although this must obviously be answered in the negative, it should be emphasized that both cytogenetic and recombinant DNA investigations provide us with very selective pictures of genomic organization. This is of concern because the higher order packing of DNA and its joining with other molecules to form chromosomal structures give rise to emergent properties, functional features that become manifest only at higher levels of complexity and that may not be deducible from the base pair composition of the DNA.A position of extrememethodological reductionismwould in our context be that the best research strategy is always to investigate the genetic changes of tumor cells at the highest possible resolution level, as alterations of genes and, ultimately, as changes in DNA primary structure. There are two fundamental differences between cytogenetic and molecular genetic techniques that make this stance untenable. First, whereas cytogenetic investigations are open‐framed (all chromosome aberrations are revealed), molecular genetic analyses are highly specific (only those aberrations are revealed that one tests for). Second, whereas the molecular approach determines the genotypic constitution of an idealized, average tumor cell, cytogenetic analysis is of real, individual cells. These may not necessarily be representative of the main population of the tumor, but at least whatever karyotypic differences exist between them are detected. Heterogeneity and clonal evolution within the tumor can thereby be assessed. This second dissimilarity is of a less principled nature than the first and should be surmountable if isolation of single cells, followed by their analysis with PCR‐based or equivalent techniques, become generally feasible methods in the molecular genetic investigation of cancers.Epistemological reductionof cancer cytogenetics to the molecular level would imply that all karyotypic findings and conclusions could be described and explained in terms of gene or, better still, DNA primary structure changes. But even in the best‐studied examples of oncogene activation through chromosomal rearrangement, heterogeneities arise in both the chromosomal and molecular domains when one focuses “up” or “down” through the various resolution levels, away from the ones providing the most explanatory and predictive power, the best fit between neoplastic phenotype and genotype. Besides this “many‐to‐many” problem, one should also be open to the possibility that the pathogenetic consequences of at least some balanced translocations and losses of chromosomal segments might be more complex than an in principle straightforward activation of oncogenes or loss of antioncogenes. Other common karyotypic anomalies, such as those involving gain of chromosome material, especially polysomies and ploidy level changes, at present have no satisfactory explanation at the gene level. It follows that in neither the methodological nor the epistemological domain has a reduction occurred, nor does one seem imminent. Both molecular‐level and chromosome‐level investigations are, and most likely will remain, indispensable for an optimal approach to the analysis of neoplastic cells. In the synthetic phase of the scientific process, the regularities and causal connections that we perceive will continue to involve descriptions both in the language of cytogenetics and in the language of molecular biology. The choices we make when shifting back and forth between the two resolution levels will depend on utilitarian, instrumentalist considerations, not on any metaphysically motivate

ISSN:1045-2257    

DOI:10.1002/gcc.2870050303

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

年代:1992

数据来源: WILEY

摘要:

AbstractWe present ten cases of posterior uveal melanoma which were karyotyped after short‐term culture. One tumour had a normal chromosome complement. The remaining nine tumours were cytogenetically abnormal, with chromosomes 3, 6, 8, 11, and 13 most frequently involved. Abnormalities of chromosome 13 were seen in two cases, chromosome 11 in three cases, and chromosomes 3, 6, and 8 in five cases. Four tumours, all derived from the ciliary body, demonstrated monosomy 3 and i(8q), confirming the involvement of these aberrations with a subgroup of uveal melanomas arising from the ciliary bod

ISSN:1045-2257    

DOI:10.1002/gcc.2870050304

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

年代:1992

数据来源: WILEY

摘要:

AbstractSchwannomas are tumors of the cranial, spinal, and peripheral nerve sheaths that originate from Schwann cells. Acoustic neurinomas are the most frequent cranial schwannomas. They might develop sporadically or in the context of neurofibromatosis type 2 (NF2). Loss of part or all of chromosome 22 is frequently found in acoustic schwannomas, suggesting that theNF2gene is a tumor suppressor gene involved in the genesis of these tumors. Only a few spinal schwannomas have been molecularly characterized so far, showing that chromosome 22 loss might also occur in these tumors. Here we present the molecular analysis of chromosome 22 in 23 acoustic schwannomas and nine schwannomas of other locations (including other cranial nerves and spinal and peripheral nerves). Most of these tumors were from sporadic cases. Multiple schwannomas of various locations were analyzed in two patients with NF2. We found partial or complete monosomy for chromosome 22 in 22% of the acoustic schwannomas and 55% of the non‐acoustic schwannomas. The tumors with partial monosomy included four with terminal deletions and one with a deletion of the centromeric part of the long arm of chromosome 22. The region between the βB2‐1 crystallin locus(CRYB2A)and the myoglobin locus(MB)was commonly deleted in these tumors. Our studies suggest that a schwannoma‐related tumor suppressor gene within this region, which might be theNF2gene, is involved in the development of schwannomas of various locations in the nervous system. Our studies indicate that the second hit in the genesis of different schwannomas within one (predisposed) NF2 patient occurs independently and via different mech

ISSN:1045-2257    

DOI:10.1002/gcc.2870050305

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

年代:1992

数据来源: WILEY

摘要:

AbstractShort‐term cultures from 19 papillary thyroid adenocarcinomas revealed clonal numerical and/or structural chromosomal changes in 13 tumors, nonclonal abnormalities in one tumor, and only normal karyotypes in five tumors. Clonal abnormalities of chromosome 10 were present in three tumors, two of which had the translocation t(7; 10)(q35;q21). Numerical abnormalities of chromosome 17 were detected in two tumor

ISSN:1045-2257    

DOI:10.1002/gcc.2870050306

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

年代:1992

数据来源: WILEY

摘要:

AbstractA combined cytogeneticand molecular analysis was performed on 11 cases of papillary thyroid carcinoma. A simple karyotypic abnormality was detected in five tumors, whereas six had no apparent chromosome change. In four of five rearranged cases the presence of a specific chromosomal abnormality involving chromosome 10 (cases 1 and 2) and chromosome I (cases 3 and 4) was associated with the rearrangement of two protooncogenes:RETandNTRKI(formerlytrk), respectively, with different donor genes. Moreover, the chromosomal localization of the involved genes and the type of chromosomal change observed suggested that RET andNTRKIactivation occurred by intrachromosomal rearrangements. The six cases with normal karyotype did not showRETorNTRKIactivation. These findings suggest that a combined cytogenetic and molecular approach would be useful in understanding the pathogenesis of thyroid neoplasia.

ISSN:1045-2257    

DOI:10.1002/gcc.2870050307

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

年代:1992

数据来源: WILEY

摘要:

AbstractHuman papilloma virus (HPV) DNA‐immortalized human mammary epithelial cells may provide a model system for studying the molecular basis of immortalization and its role in breast neoplasia. Cytogenetic analyses were performed on clones derived from HPV 16‐ and HPV 18‐immortalized human mammary epithelial cells. The majority of the clones contained near‐diploid karyotypes. The single most frequent whole‐chromosome loss was that of chromosome 19. Regions that showed preference for deletion and/or translocation included 2pter, 11qter, and 15pter. Evidence of chromosome 19 loss was confirmed by polymerase chain reaction (PCR)‐generated, chromosome 19‐specific, dinucleotide microsatellite repeat polymorp

ISSN:1045-2257    

DOI:10.1002/gcc.2870050308

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe t(6;9) associated with a subtype of acute myeloid leukemia (AML) was shown to generate a fusion between the 3′ part of theCANgene on chromosome 9 and the 5′ part of theDEKgene on chromosome 6. The same part of theCANgene appeared to be involved in a case of acute undifferentiated leukemia (AUL) as well, where it was fused to theSETgene. Genomic sequences around the translocation breakpoint were determined in two t(6;9) samples and in the case of theSET‐CANfusion. Although coexpression of myeloid markers and terminal deoxynucleotidyl transferase was shown to be one of the characteristics of t(6;9) AML, no addition of random nucleotides at the translocation breakpoint could be found. In addition, the breakpoint regions did not reveal heptamer‐nonamer sequences, purine‐pyrimidine tracts, a chi‐octamer motif, orAlurepeats. The sequence in which the translocation breakpoints occurred was enriched in A/T. Notably, the specific introns in which clustering of breakpoints occurs inDEKandCANboth contain a LINE‐1 element. As LINE‐1 elements occur with a moderate frequency in the human genome, the presence of such an element in both breakpoint regions may be more than coincidental and may play a role in the transl

ISSN:1045-2257    

DOI:10.1002/gcc.2870050309

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

年代:1992

数据来源: WILEY

摘要:

AbstractCytogenetic analysis of four ductal breast carcinomas revealed net gain of 1 q in all tumors. In the first tumor, the only change was that one chromosome 16 was replaced by a derivative chromosome consisting of 16p and 1q. The same unbalanced whole‐arm translocation was also found in the second tumor, as the only aberration in one of four abnormal clones. In the last two cases, which also were characterized by cytogenetically unrelated clones, an extra i(1q) was present in one clone in both tumors as the sole aberration. Our findings suggest that gain of 1 q is a primary chromosomal abnormality in breast carcinomas, in the sense that it is an early event that precedes the acquisition of more complex change

ISSN:1045-2257    

DOI:10.1002/gcc.2870050310

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

年代:1992

数据来源: WILEY

摘要:

AbstractMany nonrandom chromosome abnormalities have been associated with non‐Hodgkin's lymphomas (NHL). Some of these are nonspecific changes seen in many different histologic subtypes. We describe a series of abnormalities of chromosome bands 10q23–25 seen in 159 consecutive NHL patients with abnormal cytogenetic findings. The proportion of karyotypes with abnormalities of 10q varied from 3% among the immunoblastic lymphomas to 67% in the diffuse large cleaved cell lymphomas. Seventeen (10.7%) had abnormalities of 10q23–25. All but one of these were B‐cell tumors. The abnormalities consisted of six deletions and 11 translocations. Sixteen of the 17 patients had the 10q abnormality when cells were first karyotyped. The remaining patient acquired the 10q abnormality in the third of a series of biopsies. In the follicular histologic subtypes [follicular small cleaved cell (FSC), follicular mixed small cleaved and large cell (FM), and follicular large cell noncleaved (FL‐NC)], abnormalities of 10q were found in nine patients, all in association with abnormalities of 14q32. Seven of these were associated with the t(14;18)(q32;q21). Overall, 10q23–25 abnormalities were observed in 11.9% (8/67) of low‐grade [small lymphocytic (SL), FSC, and FM]lymphoma cases. DNA was available from five patients with abnormalities of 10q and was probed for rearrangements with theHOX11 (TCL3)oncogene probe. As expected, we did not find such rearrangements in these five patients with B‐cell tumors. Abnormalities of 10q23–25 have been reported previously in NHL but not

ISSN:1045-2257    

DOI:10.1002/gcc.2870050311

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

年代:1992

数据来源: WILEY