摘要:

AbstractDNA studies of the translocation t(15;17) in acute promyelocytic leukemia (APL) have shown that the retinoic acid receptor alpha (RARA) gene on chromosome 17 is juxtaposed to the promyelocytic leukemia (PML) gene on chromosome 15. ThePMLbreakpoints have been mapped to 3 clusters: bcr1, bcr2, and bcr3. We have examined thePMLbreakpoint distribution in a series of 33 Chinese patients with APL Twenty‐two patients fell within bcr1, 2 within bcr2, and 9 within bcr3. The primary structure of the reciprocal chromosome translocation joints of one patient and that of their normal counterparts have been determined and compared to those of 2 previously reported cases. These studies revealed possible topoisomerase II cleavage sites close to the breakpoints and suggested implications of DNA attachment sites to nuclear matrix. We propose that these features are relevant to the process of illegitimate recombination generating the translocation. © 1993 Wiley‐Liss,

ISSN:1045-2257    

DOI:10.1002/gcc.2870060302

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe t(14;18) chromosomal translocation characteristic of follicular lymphoma (FL) juxtaposes the immunoglobulin heavy chain locus (IGH) and theBCL2proto‐oncogene. The translocation can be readily detected as a non‐germlineNotl fragment resolved by pulsed‐field gel electrophoresis. A benefit of this approach is that it enables examination of the structure of a large region (±300 kb) surrounding the chromosomal breakpoint. In 40/46 cases the observed translocatedNotl fragment was smaller than the 680–690 kb expected from published restriction maps of the involved loci suggesting a deletion in the region of the breakpoint. Analysis of the der(14) allele by molecular hybridization demonstrated that in 35/46 cases the μ. constant region (Cμ) was deleted. Further molecular dissection of theIGHlocus demonstrated that this resulted from an interstitial deletion of the der(14) chromosome within the region defined by the μ switch region (Sμ) on the 5′ side and the ϵ constant region (Cϵ) on the 3′ end. Thus, the deletion resembled a class switch (CS) recombination event. Surprisingly, the CS deletion was as common in FL which was sIGM positive (24/33, 72.7%) as in cases where the productive allele had already undergone CS deletion (11/13, 84.6%) suggesting that the observed non‐physiologic CS deletion resulted from a cis effect of the chromosomal translocation. Similar interstitial deletions of the non‐productiveIGHallele were not seen in B cell lymphocytic lymphomas which do not have the t(14;18) translocation. Mapping of the 3′ extent of the deletion by an isotype PCR assay demonstrated frequent involvement (11/12 cases) of the γ1 constant region (Cγ1). Analysis of cases in which the deletion was not evident by Southern blotting but detectable by PCR suggested that the CS deletion had occurred in a small subpopulation of FL cells subsequent to the t(14;18) translocation. The biological role of frequent interstitial deletions of the der (14) chromosome in t(14;18)‐carrying lymphomas remains to be elucid

ISSN:1045-2257    

DOI:10.1002/gcc.2870060303

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

年代:1993

数据来源: WILEY

摘要:

AbstractInterstitial deletions of the short arm of chromosome 3 were found in short‐term cultures of five breast carcinomas (of 41 breast cancers with clonal aberrations analyzed by us during the same period). They were the only clonal structural change in three tumors; in the remaining two, the clone with 3p– coexisted with seemingly unrelated clones that had other structural and numerical aberrations. The deletions were identical, del(3)(p12p14), in four cases. The fifth tumor seemed to have a smaller deletion, interpreted as del(3)(p13p14). Our findings constitute karyotypic evidence that 3p deletions are relatively common in breast carcinomas and concur with the molecular genetic detection of loss of heterozygosity in this chromosome arm. The fact that the deletions were found as solitary changes indicates that loss of genetic information from 3p loci is an early, possibly primary, event in tumorigenesis. © 1993 Wiley‐Lis

ISSN:1045-2257    

DOI:10.1002/gcc.2870060304

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

年代:1993

数据来源: WILEY

摘要:

AbstractTransgenicWAPRASmice, obtained by infection of the constructWAPpromoter murine gene and theHRAShuman protooncogene, develop mammary adenocarcinoma within 1–3 months after pregnancy. A cytogenetic analysis was performed on 17 tumors from 10 mice. Almost all detected anomalies were chromosome gains. The resulting trisomies affected recurrently chromosomes 1, 15, 19, 17, 7, and 12, in decreasing order of involvement. Although in situ hybridization showed that the transgene was integrated in chromosome 1, the duplication of this chromosome did not depend on the presence or absence of the transgene. Comparison with human data indicates that the 3 most frequently duplicated chromosomes inWAPRASmice correspond to the human chromosome segments most frequently duplicated or amplified in breast cancer, i.e., 1q, 8q, and 11q13. None of the chromosome segments often deleted in human tumors were found to be duplicated in the mouse tumors. © 1993 Wiley‐Liss,

ISSN:1045-2257    

DOI:10.1002/gcc.2870060305

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe present molecular data to demonstrate that the isochromosome 12p, specific for human germ cell tumors (GCTs), is of uniparental origin. Eight GCT‐derived cell lines, containing one or more copies of i(12p) and/or other 12p anomalies, were analyzed with different 12p‐derived polymorphic markers. The results from Ma‐90, a near‐diploid cell line with only one i(12p) in addition to two copies of a normal chromosome 12, clearly show an allelic 12p ratio of approximately 3:1, indicating that both 12p arms are of identical parental origin. These results were further substantiated by data obtained from the other i(12p)‐positive GCT‐derived cell lines. Therefore, we conclude that the i(12p) in GCTs constitutes a genuine isochromosome with genetically identical arms. The isochromosome most likely originates from a misdivision of the centromere rather than from a translocation or a non‐sister chromatid exchange as proposed by others. We also found that supernumerary 12p copies, as observed in i(12p)‐negative GCTs, are of uniparental origin. These observations seem to point to an important role for certain 12p‐derived sequences in the development of human GCTs. © 19

ISSN:1045-2257    

DOI:10.1002/gcc.2870060306

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

年代:1993

数据来源: WILEY

摘要:

AbstractMultiple endocrine neoplasia type 2 (MEN 2) is a familial cancer syndrome arising from mutation at a locus or loci in chromosome region 10p11.2‐q11.2. The disease is characterized by medullary thyroid carcinoma (MTC) and pheochromocytoma (Pheo). To assess the genetic events in tumour initiation and progression in this disease, we have compiled an allelotype for MTC and Pheo tumours using polymorphic marker loci from each chromosome arm. Using a panel of 58 tumours, we found frequent allele losses on chromosome arms 1p (42%), 3p (30%), 3q (38%), 11p (11%), 13q (10%), 17p (8%), and 22q (29%). Loss of heterozygosity (LOH) for loci on chromosome 10 was detected in a single tumour where one whole chromosome copy was lost. We used a panel of polymorphic markers for each of chromosomes 1, 3, 11, and 17 to define a shortest region of overlap for these regions. The most frequent allele losses were on chromosome 1, spanning the entire short arm of the chromosome but not loci on 1q. LOH on chromosome 3 encompassed a minimal common region of 3q12‐qter. The regions of allelic deletion on chromosome 11(11pter‐p13), 17(17pter‐p11.2), and 13 (13q) encompass known tumour suppressor loci (WTI, TP53, RBI) which must therefore be candidates for genes contributing to MTC and Pheo development. Our data suggest allele loss on chromosome 11, 13, or 17 occurs predominantly in tumours with losses on chromosome 3, potentially reflecting the accumulation of genetic change in tumour progression. These events may be associated with more advanced disease in MTC. We suggest that at least 7 genes contribute to tumour development in MEN 2, including an initiating locus on chromosome 10 and loci on chromosomes 1, 3, 11, 13, 17, and 22 which have a progressional role in these tumours. © 1993 Wiley

ISSN:1045-2257    

DOI:10.1002/gcc.2870060307

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

年代:1993

数据来源: WILEY

摘要:

AbstractIn a series of cytogenetically analyzed renal tumors of different histological types (chromophobe carcinoma, clear‐cell carcinoma, chromophilic carcinoma, and oncocytoma) and normal renal tissue, the length of the telomeric DNA repeats was assessed using a (TTAGGG)3oligonucleotide probe. A strong correlation was noted between pronounced telomere shortening and the appearance of telomeric associations of chromosomes. These data suggest an etiologic role of the loss of telomeric DNA repeats in the formation of telomeric associations and a possible involvement of this mechanism in the pathogenesis of chromosome aberrations in human tumors. © 1993 Wiley‐Liss,

ISSN:1045-2257    

DOI:10.1002/gcc.2870060308

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

年代:1993

数据来源: WILEY

摘要:

AbstractA somatic cell hybrid containing the synovial sarcoma‐associated t(X;18)(p11.2;q11.2) derivative (der(X)) chromosome was used to characterize the translocation breakpoint region on the X chromosome. By using Southern hybridization of DNA from this der(X) hybrid in conjunction with Xp‐region specific radiation reduced cell hybrids and probes, it was found that this breakpoint maps within the ornithine aminotransferase(OAT) L1cluster. A yeast artificial chromosome (YAC) clone (OAT YAC2) which hybridizes to a human OAT cDNA probe and is known to contain part of theOATL1cluster was selected and used to confirm these results both by fluorescence in situ hybridization on synovial sarcoma patient material and by hybridization of its end‐clones to the der(X) containing hybrid cells. It was found that indeed the human Xp sequences contained within this YAC are split as a consequence of the (X;18) translocation. Therefore, we conclude that OAT YAC2 spans the synovial sarcoma‐specific translocation breakpoint and, as such, may serve as an ideal starting point from which the gene(s) involved in the development of this soft tissue tumor can be isolated. © 1993 Wiley

ISSN:1045-2257    

DOI:10.1002/gcc.2870060309

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

年代:1993

数据来源: WILEY

摘要:

AbstractCytogenetically visible gene amplification structures can consist of arrays of amplicons presumably formed by secondary “rearrangements” following amplicon formation. The structural evolution of gene amplification sites in tumor cells suggests that complex secondary structures may have some selective advantage in the tumor cell environment. Although secondary amplicon rearrangements are a hallmark of the gene amplification process, little is known about the mechanics of this process. COLO320 neuroendocrine tumor cells carry two different types of amplifiedMYConcogene sequences, one type with an intactMYCgene and the other with a rearranged “chimeric”MYCgene. We have studied various clonal subpopulations of COLO320 cells and identified regions within and downstream of theMYClocus that are unique to each amplicon type. Using double‐label fluorescence in situ hybridization with DNA probes unique to each amplicon type, we have observed that both chromosomal and extrachromosomalMYCamplicon arrays in COLO320 cells frequently consist of heterogeneous mixtures of eachMYCamplicon type. Our results suggest that the twoMYCamplicon types of COLO320 cells were formed simultaneously but independently, and that double minute chromosomes observed in COLO320 cells were formed by intermolecular homologous recombination secondary to amplicon formation. © 1993 Wiley

ISSN:1045-2257    

DOI:10.1002/gcc.2870060310

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

年代:1993

数据来源: WILEY

ISSN:1045-2257    

DOI:10.1002/gcc.2870060301

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

年代:1993

数据来源: WILEY