摘要:

AbstractChromosomal abnormalities of the 11q23 band occur frequently in various hematopoietic malignant disorders. Because numerous partner chromosomes have been previously described, it is now important to determine the number of genes involved at 11q23 and to clarify the role of the partner genes. Recent efforts in several laboratories have identified a trithorax‐related gene that is involved in most of the 11q23 abnormalities. The aim of this review is to summarize the recent data concerning these 11q23 rearrangements and the understanding of their consequence

ISSN:1045-2257    

DOI:10.1002/gcc.2870130202

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

年代:1995

数据来源: WILEY

摘要:

AbstractA protocol for comparative genomic hybridization by use of nucleotides directly labeled with fluorochromes was used to map regions of deletion and amplification in ten glioma cell lines. The protocol greatly reduced experimental artifacts. We detected several genetic aberrations, including whole chromosome loss and gain, partial loss and gain, possible isochromosome, and higher level DNA amplification. The most frequent losses (in order of frequency) occurred on chromosomes 10, 18, 13, 11, 9, 14, 4, 6, 1, and X. The most common gain occurred on chromosome 7. Several sites of previously known and unknown amplifications were observed. © 1995 Wiley‐Liss, I

ISSN:1045-2257    

DOI:10.1002/gcc.2870130203

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

年代:1995

数据来源: WILEY

摘要:

AbstractDeletion of 9p21–22 is a common genetic alteration in dysplastic, in situ, and invasive head and neck squamous cell carcinoma (HNSCC). However, a candidate tumor suppressor gene (TSG) at this site has thus far not been identified in HNSCC. We report homozygous deletion of the recently identified multiple tumor suppressor I (MTSI)/cyclin‐dependent kinase‐4‐inhibitor (CDKN2) gene mapped to 9p21, which encodes the p16 protein, a regulator of cyclin‐dependent kinase 4, in six of 16 HNSCC cell lines. We also show absence of the CDKN2 mRNA in all cell lines with CDKN2 deletion as well as in an additional two cell lines without deletion. Overall, we have identified 9p abnormalities in 12 of 16 (75%) cell lines, at least nine of which involved CDKN2. We further demonstrate that the CDKN2 deletion in HNSCC is located within a previously described region of allelic loss between D9S171 and IFNW, which spans a 4 cM region of 9p. However, examination of 36 primary tumors revealed genetic alterations in only seven of 36 (19%) tumors. These results suggest that genetic alterations at CDKN2 are frequent in HNSCC cell lines, but the role of this gene in primary tumors is less compelling. CDKN2 does not appear to be the only TSG on 9p21 in HNSCC, and our results suggest that another region of deletion exists proximal to the IFNW locus. © 1995 Wiley

ISSN:1045-2257    

DOI:10.1002/gcc.2870130204

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe t(1;19)(q23;p13) or its derivative encodes anE2A‐PBX1fusion transcript and protein that has been shown to have important prognostic and therapeutic implications in patients with acute lymphoblastic leukemia (ALL). We describe two childhood cases in which a der(22)t( 1;22)(q21‐23;p13) cytogenetically mimicked a der( 19)t( 1; 19)(q23;p 13). In one case, which was phenotyped as early pre‐B ALL with hyperdiploidy but lacked evidence of anE2A‐PBX1gene fusion by molecular study, the poor banding quality of chromosomes led to misinterpretation of the cytogenetic findings; a correct diagnosis was established only after analysis by the fluorescence in situ hybridization (FISH) method. The second case, which was classified as pseudodiploid pre‐B ALL, had both a derivative 19 and a derivative 22 but lacked sufficient cells for evaluation ofE2A‐PBX1gene fusion. This case was included in order to compare the der(19)t(1;19) and the der(22)t(1;22) and to pinpoint the difficulty in distinguishing these markers. FISH analysis can resolve diagnostic uncertainty in cases of ALL with equivocal chromosome 19 markers. © 1995 Wil

ISSN:1045-2257    

DOI:10.1002/gcc.2870130205

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe neurofibromatosis type 1 (NFI) gene encodes a tumor‐suppressor protein termed neurofibromin, which, in adults, is expressed predominantly in neurons, Schwann cells, and the adrenal medulla. Loss ofNFIgene expression has been reported in Schwann cell tumors (neurofibrosarcomas) from patients with NF1 as well as in malignant melanomas and neuroblastomas from patients without NF1. Previously, we demonstrated the lack of neurofibromin expression in six pheochromocytomas from patients with NF1, supporting the idea that neurofibromin might be an essential regulator of cell growth in these cells. To determine whetherNFIgene expression is similarly altered in pheochromocytomas from patients without NF1, we examined 20 pheochromocytomas for the presence ofNFIRNA and neurofibromin by reverse‐transcribed polymerase chain reaction (RT‐PCR) and immunohistochemistry, respectively. Reduced or absentNFIgene expression was documented in 7 of these 20 tumors (35%) including 1 of 4 sporadic tumors, 3 of 10 tumors from patients with multiple endocrine neoplasia (MEN) 2A, 2 of 4 tumors from patients with MEN2B, and 1 of 2 tumors from patients with von Hippel‐Lindau syndrome. In addition, most of these tumors expressed predominantly the type 1NFIisoform (75% type 1NFIisoform expression) as opposed to other neural crest‐derived tissues such as adrenal gland and Schwann cells, which express predominantly type 2NFI. This type 1 isoform predominance was also observed in the rat pheochromocytoma PC 12 cell line, suggesting that this change in isoform expression may be associated with the genesis of these tumors. These results collectively demonstrate that loss ofNFIgene expression is associated with progression to neoplasia in tumors originating from neural crest‐derived cells in patients without clinical manifestations of neurofibromatosis, and they support the notion that neurofibromin is a tumor‐suppressor gene product involved in the pathogenesis of a wide variety of tumor types. © 1995 W

ISSN:1045-2257    

DOI:10.1002/gcc.2870130206

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

年代:1995

数据来源: WILEY

摘要:

AbstractWe have sought to define the relationship between the proportion of marrow metaphases showing the Philadelphia chromosome (Ph) and levels ofBCR‐ABLmRNA assessed by quantitative polymerase chain reaction (PCR) in patients with chronic myeloid leukaemia (CML). From a total of 141 patients, 164 PCR assays were performed on peripheral blood samples taken within 2 weeks of a bone marrow specimen analysed by cytogenetics.BCR‐ABLmRNA was quantified in all 106 PCR‐positive samples by competitive PCR; results ranged from<10 to 3.4 × 106transcripts/μg RNA. Twenty‐one chronic‐phase patients had a median of 5.0 × 105BCR‐ABLtranscripts/μg RNA; no difference in levels of the fusion mRNA was found between 15 Ph‐positive and six Ph‐negative,BCR‐ABL‐positive patients. Ph‐positive metaphases were not detected in any individual who was PCR negative (n = 58) and in only a single patient who was PCR positive with103BCR‐ABLtranscripts/μg RNA, 30 had at least one Ph‐positive metaphase. The highest level ofBCR‐ABLtranscripts at which Ph‐positive metaphases were not detected was 1.5 × 104. For the 46 patients who had at least one Ph‐positive metaphase, a good correlation (Spearman coefficient = 0.83,P<0.0001) was found between the percentage of Ph‐positive metaphases andBCR‐ABLtranscript levels. We conclude that quantitative PCR forBCR‐ABLis an effective method for monitoring CML patients after bone marrow transplantation and is less invasive than conventional cytogenetic

ISSN:1045-2257    

DOI:10.1002/gcc.2870130207

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

年代:1995

数据来源: WILEY

摘要:

AbstractWe previously identified an anchorage independence‐suppressor gene,SAII, on rat chromosome (RNO) 5. RNO5 is homologous to human chromosomes (HSA) I and 9. In order to find the human homolog of theSAIIgene, we transferred HSAI and HSA9 to an anchorage‐independent and tumorigenic Syrian hamster BHK 191‐5C cell line by microcell fusion. For HSA9, we used a t(X; 9)‐derivative chromosome to force the retention of this chromosome in hybrids by hypoxanthine‐aminopterin‐thymidine (HAT) selection. To study the possible effect of the X portion of the der(9)t(X; 9), we also transferred a normal X to 191‐5C cells. For HSAI, a neo‐tagged chromosome was introduced. Following the transfer of der(9)t(X; 9) to 191 ‐5C cells, the hybrid cells became anchorage dependent and nontumorigenic, and, upon the loss of this chromosome, the cells regained their tumorigenic and anchorage‐independent phenotypes. The transfer of HSAX or HSAI, on the other hand, affected neither of these phenotypes. These results provide functional proof of suppressor genes on HSA9 involving both anchorage independence and tumorigenicity. In addition, our data suggest the presence of another gene on HSA9 that causes a negative growth effect and whose phenotypic expression, contrary to the suppressor genes, is dosage dependent. ©

ISSN:1045-2257    

DOI:10.1002/gcc.2870130208

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

年代:1995

数据来源: WILEY

摘要:

AbstractPolymerase chain reaction (PCR)‐directed sequence analysis was performed to characterize the genomic and cDNA breakpoint junctions of t(11; 22) (q24; q12) translocation in a case of Ewing's sarcoma, in which theEWSgene located on chromosome 22 is rearranged with theFLIIgene located on chromosome 11. RNA‐PCR revealed the novel chimeric product ofEWS/FLIIgene on the derivative chromosome (der) 22, resulting from a probable fusion ofEWSexon 7 toFLIIexon 9. Sequencing of the PCR‐amplified genomic fragments of the fusion genes showed that the breakpoints on der(22) occurred inEWSintron 7 and, most probably, inFLIIintron 8. Those of the untranxribed counterpart on der(11) were located in the sameFLIIintron and inEWSexon 11, with deletion of a considerable amount of sequences from both genes. These findings indicate asymmetric junction at the molecular level in the present t(11; 22). None of the reported conserved sequences that mediate other cancer chromosome translocations was observed around the genomic junctions. Instead, a palindromic hexamer 5′‐GCTAGC‐3′ was found to flank the breakpoints of both genes on der(22), which may have a functional significance in the genesis of the t(11; 22). © 1995 W

ISSN:1045-2257    

DOI:10.1002/gcc.2870130209

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

年代:1995

数据来源: WILEY

摘要:

AbstractA reciprocal translocation, t(10; 22) (q22; q11), resulting in a masked Ph chromosome was identified in a patient diagnosed with chronic myeloid leukemia (CML). Both homologs of chromosome 9 were of the normal pattern. Two signals for theABLprobe, both of them hybridized to chromosome 9, were demonstrated via fluorescence in situ hybridization (FISH). Furthermore, cohybridization with two differently labeledBCR/ABLtranslocation DNA probes indicated aBCR/ABLfusion apparently located on 9q34. Molecular studies revealed a rearrangement of theBCRregion and expression of a chimericBCR/ABLmRNA of CML configuration. These findings indicate that theBCR/ABLfusion resulted from an unusual relocation of theBCRgene from its normal position on 22ql I to 9q34 adjacent to theABLgene.

ISSN:1045-2257    

DOI:10.1002/gcc.2870130210

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

年代:1995

数据来源: WILEY

摘要:

AbstractPrevious analysis of the monoblastic cell line U937 has shown that several sublines contain a rearranged chromosome arm I I q. In order to determine the true nature of the rearrangement, fluorescence in situ hybridization (FISH) was carried out with various combinations of single copy anonymous markers, clones containing genes, a chromosome 10 paint, and an I I centromere specific sequence. The rearrangement was deduced to be a reciprocal translocation between chromosomes 10 and 11 described as t( 10; 11 )(p 13‐ 14;q 14‐21 ). The breakpoint on chromosome 11 is telomeric to the /NT2 gene and the pHS11 probe at 11 q 13, and centromeric to the marker D 11536 localized to 11q 14.3‐q22. 1 and the MLL gene at 11 q23. Similar translocations have been reported in various acute leukemias, principally of the monocytic lineage, and also in T‐cell precursor acute lymphocytic leukemias. Further characterization of the genetic rearrangements in U937 may lead to the isolation of genes important in leukemogenesis and provide an in vitro system for their study. © 1995 Wiley

ISSN:1045-2257    

DOI:10.1002/gcc.2870130211

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

年代:1995

数据来源: WILEY