摘要:

AbstractEwing's sarcoma (ES) and peripheral neuroepithelioma (PN) are related tumors, possibly of neural crest origin, which are cytogenetically characterized by the specific translocation t(11;22)(q24;q 12). The cos5 locus, previously identified in the vicinity of the chromosome 22 breakpoint of this translocation, was shown by in situ hybridization on interphase nuclei to lie betweenVIIIF2andLIF, two loci located on either side of the breakpoint and at a distance of less than 2,000 kb. The progressive expansion of this locus by chromosome walking led to the construction of a 300 kb contig, which finally crossed the breakpoint. The subsequent cloning of the two translocation junction fragments of a PN, followed by the molecular characterization of the translocation breakpoints of 20 ES and PN, showed that most chromosome 22 breakpoints are clustered within a small, 2 kb region. In contrast, the chromosome 11 breakpoints are scattered over a region of at least 40 kb. The translocation leads to the synthesis of a chimeric transcript that links sequences from chromosomes 22 and 11. Finally, no evidence was found of any specific difference in the position of ES and PN translocation breakpoints.

ISSN:1045-2257    

DOI:10.1002/gcc.2870050402

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

年代:1992

数据来源: WILEY

摘要:

AbstractMost myxoid liposarcomas (MLS) are characterized cytogenetically by a t(12; 16)(q13;p11). It is reasonable to assume that this translocation corresponds to the consistent rearrangement of one or two genes in 12q 13 and/or 16p11, and that the loci thus affected are important in the normal control of fat cell differentiation and proliferation. We have used Southern blot technique to test whether a gene of the CCAAT/enhancer binding protein (C/EBP) family,CHOP, which maps to 12q13 and is assumed to be involved in adipocyte differentiation, could be the 12q gene in question. Using a cDNA probe that spans theCHOPcoding region, we detected one rearranged and one wild type allele in nine of nine MLS with t(l2;l6). Using PCR generated, site‐specific probes corresponding to the non‐coding exons 1 and 2 and intron 2 ofCHOP, rearrangements in five of seven tumors mapped to the 2.4 and 1.6 kbp Pstl fragments that contain the first two exons and introns of the gene and the upstream promoter region. In contrast to the findings in MLS, no tumor without a t(12;16) exhibited aberrantCHOPrestriction digest patterns. These tumors included one highly differentiated liposarcoma with abnormal karyotype but no involvement of 12q 13, seven lipomas with various cytogenetic aberrations of 12q 13–15, two uterine leiomyomas with t( 12; 14) (q 14–15;q23–24), and one hemangiopericytoma and one chondroma, both of which also had 12q 13 changes. These findings demonstrate that the 12q breakpoint of the t( 12;16) in MLS differs from those in the other tumors investigated, even in cases with no cytogenetically visible differences in breakpoint position, thatCHOPrearrangement is specific for MLS, and that the breakpoints cluster to the 5′ region of the gene. We assume that theCHOPalteration is an important step in MLS tumorigenesis and speculate that this is achieved by interference with the normal function of the C/EBP family of transcript

ISSN:1045-2257    

DOI:10.1002/gcc.2870050403

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

年代:1992

数据来源: WILEY

摘要:

AbstractSeveral cytogenetic lesions in chromosomes 2, 5, 12, and 16 have been repeatedly coselected with in vitro macrophage differentiation in a clonal murine thymic tumor cell line. Parental‐type subclones, which show an extremely immature hemopoietic phenotype, do not carry the aberrations. The frequency of the stable differentiated variants is elevated by 5‐azacytidine and bromodeoxyuridine, consistent with chromosome breakage being responsible for the phenotype. The frequency is also raised by dexamethasone. Since variants are 300–3,000‐fold more resistant to dexamethasone than parental clones, we interpret this to be largely due to selection. Three of the lesions, on chromosome 2, match those previously described as associated specifically with in vivo‐generated murine myeloid tumors, induced by X irradiation and corticosteroid treatment. Several implications follow from these observations. (I) In vitro differentiation in clonal tumor cell lines can be used to select for tumor‐associated lesions. This should allow genetic and molecular analysis of the chromosome 2 lesions and of others that may pinpoint genes critical to macrophage differentiation and transformation. (2) Myeloid and lymphoid tumors that occur in response to X irradiation may diverge from a common initiating tumor. (3) The hemopoietic lineage switch phenomenon, previously described by several authors, may be caused by similar or identical chromosome

ISSN:1045-2257    

DOI:10.1002/gcc.2870050404

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

年代:1992

数据来源: WILEY

摘要:

AbstractRhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and accounts for 10% of all solid tumors in children. There are three different histologic forms of this tumor: embryonal (RMS‐E), alveolar (RMS‐A), and primitive (RMS‐P). Among these, the embryonal form has responded well to chemotherapy. Identification of the correct subtype is important for both the management and treatment of this malignancy. However, the histopathologic classification of RMS is sometimes difficult and distinguishing between the embryonic and primitive forms can present a diagnostic dilemma. Chromosomal abnormalities have been observed in all subtypes. We present the cytogenetic findings in six cases of RMS or related sarcoma. All four cases with RMS‐A had both numerical and structural abnormalities in the tumor and involved bone marrow specimens. Three patients had a common marker, t(2;13)(q37;q14), and one patient had a variant marker involving 13q14, t(1;13) (p36;q14), and double minutes (dmin). The single embryonal RMS patient had modal chromosome numbers in the hypertriploid range and extensive structural abnormalities; the t(2; 13) was not present, but translocation of 13q to both I q and 2p was observed, der(l)t(l;l3)(q21;q14) and der(2)t(2;13)(p25;q14). The patient with primitive type RMS had a hypodipl‐oid line with several markers, including a complex translocation involving chromosomes 5 and 13 with a breakpoint at 13q14, and t( 11;22)(q24;q 12), a chromosome marker heretofore found only in Ewing's sarcoma and related tumors. This patient had atypical RMS with mixed neural and myogenic elements. The significance of these chromosomal markers and their importance in the characterization of childhood tumors are discussed, along with a review of the literature. Published 1992 by Wiley

ISSN:1045-2257    

DOI:10.1002/gcc.2870050405

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe development of human breast cancer is characterized by a variety of genetic alterations, and cytogenetic analyses have documented the consistent involvement of both arms of chromosome I. In the present study, molecular markers detecting restriction fragment length polymorphisms were used in pairwise screening of normal and tumor DNA to determine the frequency of allelic imbalance in breast tumors. Loss of heterozygosity (LOH) in the polymorphic epithelial mucin(PEMorMUCI) gene at 1q21 was found in 16% of 89 informative (constitutionally heterozygous) cases, whereas gain in intensity of one allelic band was more frequent (37%), a total of 47% of cases manifesting either allelic loss or gain. Three additional tumors manifested a structural alteration. Allelic loss or gain in thePEMgene was not associated with other prognostic factors, e.g., tumor size, lymph node status, steroid receptors, DNA ploidy, S phase fraction, protooncogene amplification, histological type, or patient age. However, LOH in thePEMgene was significantly correlated with early disease recurrence (P = 0.006). LOH on 1p was found in 27% of 117 informative cases, using probes for either DIS57 or DIZ2 located at 1p33‐p35 and 1p36, respectively. Somatic allelic imbalance on 1p and 1q seemed to be independent events and not the effect of loss of a whole chromosome 1. LOH on 1 p was significantly correlated to the presence of lymph node metastasis, to larger tumor size, and to DNA nondiploidy, but no correlation was found to disease outcome at this limited duration of follow‐up (median 29 months). ©1992 Wiley‐Lis

ISSN:1045-2257    

DOI:10.1002/gcc.2870050406

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe disease ataxia telangiectasia (A‐T) is a multifaceted disorder in which patients have an increased chance of developing a T‐cell leukaemia, often with abnormalities of chromosome 14, but sometimes with rare translocations, like t(X; 14)(q28;q11). We describe the cloning of the breakpoint of one such novel t(X;14) from an A‐T patient. The translocation breaks within the T cell receptor α chain gene on chromosome 14 at band q11 and in a region of the X chromosome, within about 1 Mb of the telomere of the long arm. The patient subsequently developed T‐cell prolymphocytic leukaemia (T‐PLL), and molecular examination showed that the tumour cells carried the same t(X; 14) breakpoint as that cloned from the premalignant cells. The same breakpoint could be detected in blood samples taken as much as 5 years prior to diagnosis of T‐PLL. This suggests a role for the abnormality in the tumour development in this patient but implies that other mutational events were necessary for overt disease to become manifest. © 1992 Wi

ISSN:1045-2257    

DOI:10.1002/gcc.2870050407

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

年代:1992

数据来源: WILEY

摘要:

AbstractLoss of heterozygosity (LOH) for polymorphic markers is a frequently occurring event in some tumors, reflecting the role of allele loss in the development of these tumors. We have determined LOH in 38 cases of Wilms tumor for the 2 known loci on chromosome arm 11p and for a newly detected locus on chromosome arm 16q. Only 7 of the 38 tumors studied showed reduction to homozygosity of 11p13 markers. In 4 of these tumors, reduced expression ofWTIandWITI, genes located at 11p13 and implicated in Wilms tumorigenesis, was noted. However, this was also found in 2 of 7 tumors showing LOH exclusively of 11p15 markers and in 15 of the remaining 24 tumors in which there was no LOH for 11p markers. This suggests that events not involving mitotic recombination or chromosome nondisjunction are the most common mechanisms for mutations at the 11p Wilms tumor locus. We also noted that mitotic recombination involving 11p15 loci occurred in addition to reduced expression of the 11p 13 locus genes in 2 tumors, suggesting a possible interaction between these 2 loci. In addition, LOH for 16q markers was observed in 6 tumors. In one case this was coincident with reduction ofWTIandWITIgene expression, and in 3 other cases it occurred in addition to 11p LOH. This indicates that an additional locus on 16q is likely to be involved in Wilms tumorigenesis. © 1992 Wiley‐Liss, I

ISSN:1045-2257    

DOI:10.1002/gcc.2870050408

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

年代:1992

数据来源: WILEY

摘要:

AbstractMicrocell‐mediated chromosome transfer (MMCT) is a powerful genetic technique that permits the transfer of a single chromosome from one mammalian cell to another. The utility of MMCT for gene mapping strategies is critically dependent on the careful characterization of the chromosomes being transferred. We have recently reported the identification of a single rearranged human chromosome, designated Tneo, which corrects the UV sensitivity and excision repair defect of cells of xeroderma pigmentosum genetic complementation group D (XP‐D) in culture (Flejter WL et al., Proc Natl Acad Sci USA 89:261–265, 1992). Additionally, those studies demonstrated a role for the excision repair cross‐complementing 2 (ERCC2) gene in the observed phenotypic correction. We now report the results of detailed conventional and molecular cytogenetic characterization of the complementing Tneo chromosome. This analysis revealed a complex rearrangement involving material from human chromosomes 16, 17, and 19. Characterization of deletions of Tneo which retained or lost XP‐D complementing ability mapped the gene responsible for phenotypic correction to a small region of the terminal q‐arm of this chromosome. This region includes the previously described human DNA repair gene cluster located in the region 19q13.2‐q13.3, a result consistent with the notion that the in vitro correction of XP‐D cells by the Tneo chromosome is rendered by dieERCC2locus. The data illustrate the potential value of detailed cytogenetic characterization of a human chromosome present in a somatic cell hybrid, even when that material involves complex

ISSN:1045-2257    

DOI:10.1002/gcc.2870050409

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

年代:1992

数据来源: WILEY

摘要:

AbstractProteins encoded by homeobox containing genes are sequence‐specific DNA binding proteins implicated in the control of gene expression in both developing and adult tissues. Two recently characterized human homeobox genes,HB9andHB24, are highly expressed in CD34‐positive marrow cells but not in CD34‐depleted marrow cells, Their expression is readily down‐regulated during the differentiation of hematopoietic progenitors to specific cell lineages. In this study, genomic DNA fragments isolated withHB9(3 kb) andHB24(6 kb) cDNAs were used to map their chromosomal location by fluorescence in situ hybridization. BothHB9andHB24DNA probes gave specific hybridization signals on chromosome 1. The hybridization loci were identified by combining fluorescence images of the probe signals with fluorescence banding patterns generated by cohybridization in situ with an Alu probe (R‐like banding) and by DAPI staining (G‐like). The results demonstrate that the loci of theHB24andHB9genes are within bands 1q41–q42.1. A cohybridization experiment utilizing both probes with two‐color fluorescence imaging could not resolve separate loci for the two genes. © 1992

ISSN:1045-2257    

DOI:10.1002/gcc.2870050410

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

年代:1992

数据来源: WILEY

摘要:

AbstractCytogenetic and/or loss of heterozygosity studies were performed on 13 ependymomas, 11 pilocytic astrocytomas, and 18 oligodendrogliomas. Loss of chromosome 22 was the most frequent genetic abnormality among the ependymomas. We found no consistent genetic abnormality in pilocytic astrocytomas. The most common genetic abnormality in oligodendrogliomas was loss of a portion of chromosome 19. Each informative oligodendroglioma had loss of alleles mapped to the long arm (q) of chromosome 19. One oligodendroglioma had an apparent homozygous deletion of the D19S8 locus. Our results, when combined with those in the literature, indicate that chromosomes 9, 11, and 22 may harbor genes important for the pathogenesis of ependymomas and that 19q probably harbors a gene important for the pathogenesis of oligodendrogliomas. © 1992 Wiley‐Liss, I

ISSN:1045-2257    

DOI:10.1002/gcc.2870050411

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

年代:1992

数据来源: WILEY