摘要:

AbstractDeletions of the short arm of chromosome II have been identified by both cytogenetic and molecular criteria in bladder and other types of solid tumor, indicating the presence of one or more suppressor loci in this region. To localize the II p deletion target(s) more precisely and to screen for loss of heterozygosity (LOH) on the long arm of the chromosome, I00 bladder tumors were analyzed for LOH on chromosome II using restriction fragment length polymorphism (RFLPs) and microsatellite markers mapped to both II p and II q. Thirty‐four tumors were found to have LOH at I or more loci. Of these, I7 had LOH restricted to II p, I3 had LOH of both II p and II q, and 4 had LOH of II q only. Eight tumors showed LOH at all informative loci indicating probable loss of an entire copy of chromosome II. A common region of deletion was defined on II p between DIIS922(IIpI5.5) and DlIS569 (IIpI5.I‐I5.2). This region does not include theHRASorWTIloci (at IIpI5.5and IIp13, respectively). Seventeen tumors had LOH on II q, 4 of which had LOH on II q only. The common region of deletion on II q was betweenFGF3and DI IS490 (IIq I3‐q23.2). Two tumors showed LOH on both II p and II q with a clear region of retention of heterozygosity between, indicatinn the existence of two deletion targets on chromosome II. © 1995 Wiley‐L

ISSN:1045-2257    

DOI:10.1002/gcc.2870130102

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

年代:1995

数据来源: WILEY

摘要:

AbstractTwo molecular defects have been described in parathyroid adenomas: rearrangement and overexpression of thePRADI/cyclin DI oncogene and allelic loss of chromosome II DNA, often including the multiple endocrine neoplasia type I (MENI) putative tumor suppressor gene region. In an effort to identify additional parathyroid tumor suppressor genes, we examined 25 parathyroid adenomas for tumor‐specific allelic loss of polymorphic DNA loci located near known or candidate tumor suppressor genes. Control leukocyte DNA from all 25 patients was heterozygous for I or more of the 9 chromosome I markers examined. Allelic loss at I or more of these informative loci on chromosome I was observed in 10 of 25 (40%) adenomas. Although many tumors lost extensive regions on chromosome I, all but one of these tumors had allelic loss of distal I p (I p32‐pter); four tumors also lost loci on Iq. Allelic loss at IIqI3, the site of the MEN I gene, was detected in 5 of 2I (24%) informative cases, including 3 with Ip loss. In contrast, allelic loss was rarely observed at loci on 99 and Iop and was not observed at loci on 3p, 3q. 4p, 5q, I2q, I4q, I8q, 22q, or Xp. In summary, clonal allelic loss of loci on chromosome arm Ip is a frequent feature of parathyroid adenomas, implying that inactivation of a tumor suppressor gene(s) on Ip commonly contributes to their pathogenesis. © 1995 Wiley‐Lis

ISSN:1045-2257    

DOI:10.1002/gcc.2870130103

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

年代:1995

数据来源: WILEY

摘要:

AbstractPresumptive tumor suppressor genes may be localized to specific chromosomes by the procedure of microcell fusion, whereby individual chromosomes derived from normal human cells are introduced into tumor cells. Allelic loss on chromosome I 8 is commonly seen in endometrial carcinoma, and theDCCgene on chromosome arm 18q is a potential human tumor suppressor gene. In this study, we investigated the hypothesis that a gene on chromosome 18, possiblyDCC, is capable of suppressing the tumorigenicity of endometrial carcinoma cells. Microcells from the mouse A9 cell clone containing one human chromosome I8 tagged with the pSV2‐neo plasmid were fused with the highly tumorigenic endometrial carcinoma cell lines HHUA and Ishikawa, and G418‐resistant microcell hybrids containing an extra copy of chromosome I8 were isolated. Clones isolated from the HHUA cell line were completely suppressed for tumorigenicity in nude mice, and clones from the lshikawa line were suppressed or inhibited for tumorigenicity. In contrast, growth rates in vitro were not significantly affected in clones from either parental cell line. DCC expression was elevated in most of the suppressed hybrids. These results indicate that a gene on human chromosome I 8 is capable of suppressing the tumorigenicity of endometrial carcinoma cells, and that DCC is a candidate for this endometrial carcinoma tumor suppressor gene. © 1995 Wiley‐Lis

ISSN:1045-2257    

DOI:10.1002/gcc.2870130104

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe t(8; 21) is a common chromosomal abnormality, preferentially associated with acute leukemia showing features of myeloid differentiation. Recently, two genes–AMLIwhich has a unique runt domain, andETO(MTG8)–have been isolated from the chromosomal breakpoint. In this study, we isolated and identified two fused transcripts from a leukemic cell line carrying t(8; 21).AMLIandETOwere fused at the same position in these transcripts. One of the transcripts codes a unique domain, including two zinc finger domains and three proline‐ and one leucine‐rich region. The other transcript codes only for one proline‐ and leucine‐rich region but lacks zinc finger domains. We demonstrated by polymerase chain reaction (PCR) analysis that I) these two transcripts are consistently expressed in leukemic cells with t(8; 21) obtained from patients and 2) expression ofAMLIwas not restricted to the particular stage of hematopoietic differentiation but was present in all hematopoietic cells investigated. We also provide evidence that two wild types ofETOtranscripts containing the region of theETOgene in fused transcripts are expressed in hematopoietic cells from different lineages. The widespread expression ofAMLIandETOin hematopoietic cells suggests a fundamental role of these proteins in hematopoiesis. Furthermore, the differences in the carboxy termini ofETOmay modulate the activity of fused proteins resulting from the chromosomal translocation t(8; 21). © 1995 Wil

ISSN:1045-2257    

DOI:10.1002/gcc.2870130105

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

年代:1995

数据来源: WILEY

摘要:

AbstractChromosome rearrangements involving chromosome I, band p36, are among the most common aberrations in non‐Hodgkin lymphomas (NHL). We have studied nine cases of NHL with add(I)(p36) using fluorescence in situ hybridization (FISH) from a series of 205 cases. Five were follicular low‐grade NHL and four were follicular or diffuse high‐grade NHL. Three of the five cases with follicular low‐grade NHL did not contain the 14; 18 translocation. The extra material on the add(l)(p36) in these three cases was derived from chromosome segment 2q31‐qter; in one it was observed as a sole clonal rearrangement. In the two remaining cases, with t(14; 18), the add(l)(p36) consisted of material from chromosome arms 3q and 17q, respectively. In the four cases of high‐grade NHL, the material added on to I p36 was derived from chromosomes 6, 9, 17, and 19, respectively. Using a I p36‐specific probe, DIS94, we showed a deletion on the add(I) in one of the cases with low‐grade NHL, whereas no loss was observed in one of the cases with high‐grade NHL. Our study indicates that cytogenetically similar add(l)(p36) are found in both high‐ and low‐grade NHL, and the breakpoint on Ip36 as well as the origin of translocated material may vary.

ISSN:1045-2257    

DOI:10.1002/gcc.2870130106

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe relatively frequent loss of heterozygosity at loci on the short arm of chromosome 11 in human lung cancers has suggested the presence of a putative tumor suppressor gene. For location of the gene, a fine deletion map of human chromosome 11 was constructed by analysis of DNAs from 79 lung cancers with 31 sequence‐tagged‐site markers that dotted chromosome 11 and detected polymorphic changes in nucleotide sequences. The results showed that three regions, 11p 12‐p 15, 11q12, and 11 q14‐q24, were commonly deleted in a considerable number of cancers, indicating the possible presence of more than one tumor suppressor gene. The range of deletion in the 11p15 region was estimated to be 4.5 megabases. That in the 11q24‐q24 region was divided into two portions: one was 3 cM in length, and the other was longer and could not be specified because of lack of appropriate markers. The deletion in the 11q12 region was so short that two markers flanking the region could not be identified by genetic analysis. © 1995 Wiley

ISSN:1045-2257    

DOI:10.1002/gcc.2870130107

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

年代:1995

数据来源: WILEY

摘要:

AbstractLoss of heterozygosity (LOH) of mouse chromosome 7 has been consistently demonstrated in chemically induced murine squamous cell carcinomas (SCCs). The region of this chromosome presenting LOH in the mouse tumors is syntenic to human chromosome segments II p I5 and II q. To determine whether the introduction of human chromosome (Hchr) II can suppress the growth of murine SCC, we injected four clones of a chemically induced murine SCC cell line bearing an Hchr II into athymic BALB/c nude mice. All microcell hybrid clones with Hchr II (CH721Hchr II) had latency periods twice as long as those of the parental CH72 cells and control hybrids containing a Hchr 12. Tumor‐derived cells from CH721Hchr II hybrids had lost centromeric and telomeric sequences from Hchr II. All repressed cell lines grew significantly m e slowly in vitro than did the controls. These results suggest that Hchr II contains a tumor‐suppressor gene capable of inhibiting tumorigenicity in chemically induced SCC, confirming common pathways in the development of human neoplasias and the murine model. © 1995 Wiley‐Lis

ISSN:1045-2257    

DOI:10.1002/gcc.2870130108

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

年代:1995

数据来源: WILEY

摘要:

AbstractLoss of chromosome 20 and rearrangement of the short arm of chromosome 9 were identified by banding analysis of three adult patients with acute lymphoblastic leukemia (ALL). The G‐banding pattern suggested and identical deletion of 9p, but, also, an unbalanced translocation with chromosome 20 was taken into consideration. Dual‐color chromosome painting with probes for chromosomes 9 and 20 revealed the presence of material from chromosome 20 at the short arm of the abnormal chromosome 9 in all three cases. Centromeric alpha‐satellite DNA of both chromosome 9 and chromosome 20 was demonstrated by fluorescence in situ hybridization and indicated the presence of a dicentric chromosome. The hybridization of a YAC clone of the short arm of chromosome 20 proved that the dicentric chromosome contained the short arm of chromosome 20, which had been suspected from the G‐banding pattern. Thus, the rearrangement was interpreted as dic(9; 20)(pl I;qi I . ? I). Because this was the sole chromosome abnormality in two patients, dic(9; 20) may be a primary chromosome aberration in ALL. In one case, a 9q+chromosome derived from a Philadelphia (Ph) translocation was involved in the formation of the dicentric chromosome. Immunophenotyping revealed CD 1o+B‐cell precursor ALL in all three cases. Whereas the two patients in whom dic(9; 20) was the sole cytogenetically detectable change are in continuous complete remission for 10 and 45 months, respectively, the Ph+patient relapsed with leukemia and died 8 months after diagnosis. © 1995 Wiley

ISSN:1045-2257    

DOI:10.1002/gcc.2870130109

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

年代:1995

数据来源: WILEY

摘要:

AbstractLiterature on the cytogenetics of dermatofibrosarcoma protuberans (DFSP) is limited; only I0 cases with chromosome aberrations have been reported. They are karyotypically characterized by the presence of supernumerary ring(s), either as the sole cytogenetic abnormality or together with a few additional structural or numerical changes. We report the cytogenetic and fluorescence in situ hybridization (FISH) analysis of three new DFSP, one primary and two recurrent tumors. In two cases we found a supernumerary ring as the sole change, whereas the third had two copies of a marker chromosome and monosomy of chromosome 22. Sequences of chromosomes I7 and 22 were identified by FISH in the supernumerary rings and in the markers. The fluorescence pattern suggested that additional sequences were present in the two rings, but showed that the marker chromosomes were entirely painted by chromosome 17 and 22 probes. The findings indicate that juxtaposition and/or amplification of chromosome 17 and 22 sequences could be crucial in the pathogenesis of DFSP. © 1995 Wiley‐Liss, I

ISSN:1045-2257    

DOI:10.1002/gcc.2870130110

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

年代:1995

数据来源: WILEY

摘要:

AbstractA reciprocal t(I; 15)(p36.1–36.3;q25‐26) has been identified in an established neuroblastoma cell line (NGP) that earlier studies had shown to carry, among others, a rearrangement at the Ip subtelomeric region. Though it has not been possible to establish whether this translocation was constitutional, it is of interest to note that one of the breakpoints is located within the well‐known Ip consensus site of tumor‐associated chromosomal rearrangements where, as a result of the reciprocal translocation, theFESoncogene has been transferred from autosome IS. It is to be expected that the molecular cloning of the I p and I 5q translocation breakpoints may yield crucial data for understanding the association between specific chromosomal rearrangements and malignant tumor prog

ISSN:1045-2257    

DOI:10.1002/gcc.2870130111

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

年代:1995

数据来源: WILEY