摘要:

AbstractTranslocations in bands 11q23.3–11q24 are associated with several human cancers, including acute lymphoid and acute myeloid leukemias (AML) and Ewing's sarcoma. We have characterized two independent deletions in this region, one derived from a patient with AML who previously had a T‐cell lymphoma, and another from a Wilms' tumor patient. Cytogenetic analysis of the ML‐2 cell line established from the malignant cells of the AML patient indicated that one chromosome 11 homolog had an interstitial deletion, del(11) (q23q24), and the remaining homolog was involved in a recurring translocation, t(6;11) (q27;q23). According to karyotype analysis on the Wilms' tumor patient (EH), one chromosome 11 was normal and the other carried an interstitial deletion at 11q23.3–11q25. Somatic cell hybrids segregating the EH deletion (EHR4) and the ML‐2 deletion (MLR4) have been isolated. The EH deletion is distal to theMLLprobe recently associated with 11q23.3 leukemia breakpoints (Ziemin‐van der Poel et al.: Proc Natl Acad Sci USA 88:10735–10739, 1991). The ML‐2 deletion could involve theMLLgene at a point distal to other breakpoints withinMLLBoth deletions include the Ewing's sarcoma breakpoint at 11q24.1. By Southern blot analysis we identified three anonymous DNA markers (D11S272, D11S273, and D11S219) and theETS1oncogene, which map within each deleted region. These markers are conserved based on zoo blot analysis, and they are valuable for physical mapping and genetic characterization of a region that may code for gene products associated with growth control and tumor suppression in a variety of cancers. © 1993

ISSN:1045-2257    

DOI:10.1002/gcc.2870070202

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe previously proposed that a local duplication, not the loss of the subsequently amplified marker from its original site, might be the first step in gene amplification in human cells. It is important to investigate this issue in naturally occurring amplification and when copy numbers are relatively low. We have examined the location of single‐copy and amplified 11q13 sequences in cell lines from human breast cancers and squamous cell carcinomas using fluorescence in situ hybridization both with a probe specific for the 11q13 amplifying region and with a chromosome 11‐specific library. We show that in most cell lines the 11q13 amplicons are physically linked to chromosome 11 or to a chromosome derived from chromosome 11 by various rearrangements near the 11q13 region. In none of the cell lines were interstitial deletions of 11q13 detected. These results indicate that 11q13 amplification in human tumor cells generally does not involve deletion as the initial step. One cell line with chromosomally located amplified 11q13 sequences contained double minutes that harbored theMYCgene but no 11q13 sequences. This suggests that the genetic outcome and the mechanism of gene amplification are probably dependent on specific DNA sequences rather than on the origin of the cells. © 1993 Wiley‐Lis

ISSN:1045-2257    

DOI:10.1002/gcc.2870070203

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

年代:1993

数据来源: WILEY

摘要:

AbstractFrequent losses of heterozygosity observed at several chromosomal loci in primary lung cancers have indicated the existence of several tumor suppressor genes associated with this type of cancer. We have examined loss of heterozygosity on chromosomal arm 8p in 49 cases of non‐small cell lung carcinoma, using 14 restriction fragment length polymorphism markers. Of 42 cases informative with at least one marker, 21 showed allelic loss, including 15 of 32 adenocarcinomas and 5 of 9 squamous cell carcinomas. The frequency of allelic loss on 8p was similar at all clinical stages. Deletion mapping defined a single common region of deletion in these tumors within an 8 cM interval at 8p21.3–p22 flanked by the loci defined by cMSR‐32 and cC18–245. © 1993 Wiley

ISSN:1045-2257    

DOI:10.1002/gcc.2870070204

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

年代:1993

数据来源: WILEY

摘要:

AbstractPRAD1(previously D11S287) is a putative proto‐oncogene at 11q13, activated by overexpression through gene rearrangement or gene amplification in several types of human tumors including parathyroid adenomas, centrocytic lymphomas and other B‐cell tumors with t(11;14), and breast cancers.PRAD1(alsoCCND1) encodes cyclin D1, which may regulate the G1‐S phase transition in the cell cycle. Here, we report the cloning and characterization of the chromosomalPRAD1/cyclin D1 gene and the sequence of its promoter region. The gene spans about 15 kb and has 5 exons; its promoter region has Sp 1 binding sites and no obvious TATA box, characteristics of housekeeping genes and growth‐regulating genes. Furthermore, an E2F binding motif present close to the major transcription start site may be involved in cell cycle‐dependent expression of this gene. We also report the sequence of DNAs spanning joining regions of a reciprocal parathyroid hormone/PRAD1gene rearrangement in a parathyroid adenoma. Comparison with normal sequences suggests that the rearrangement was not a simple break‐and‐ligate event, but rather involved multiple steps, including two microdeletions and a microinversion. Very short sequences conserved near the breakpoints and symmetrical elements in the eventually inverted DNA segment might have played a role in this illegitimate complex recombination, which may have similarities with a constitutional translocation in Duchenne muscular dystrophy. © 1993 W

ISSN:1045-2257    

DOI:10.1002/gcc.2870070205

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

年代:1993

数据来源: WILEY

摘要:

AbstractDeletions within the short arm of the human chromosome 11 have been found to be involved in the genesis of several tumours, including different urogenital neoplasms. We have studied 31 male germ cell tumours (19 seminomas and 12 nonseminomas), and observed loss of heterozygosity at 11p loci in 40% (12/30) of these tumours [35% (9/26) at 11p13 and 31% (8/26) at 11p15]. Our data suggest that inactivation of one or more tumour suppressor genes on 11p are involved in the genesis of testicular cancer. In addition, identification of the parental origin of the allelic losses revealed a paternal loss in six patients and a maternal loss in one case. © 1993 Wiley‐Liss, I

ISSN:1045-2257    

DOI:10.1002/gcc.2870070206

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

年代:1993

数据来源: WILEY

摘要:

AbstractHuman neuroblastomas are characterized by cytogenetic and molecular analysis as frequently containing deletions of distal 1p. Loss of heterozygosity (LOH) studies have localized a region of shared deletion to 1p35–36.1. Using the single‐strand conformation polymorphism (SSCP) technique, we developed polymorphic assays for two genes, the amiloride‐sensitive Na+/H+antiporter(APNH)and tumor necrosis factor receptor 2(TNFR2)genes, which map to this region. We used these SSCPs to detect LOH in a panel of neuroblastomas. Allelic loss was readily detected in 8 of 39 informative tumors. The SSCP‐derived LOH results were consistent with LOH results generated from a set of distal 1p probes that identify restriction fragment length polymorphisms (RFLPs). TheAPNHlocus could be excluded from the region of consistent deletion, but theTNFR2locus could not be excluded. We conclude that the SSCP technique is a precise and efficient method for detecting LOH in human neoplasia. © 1993 Wiley

ISSN:1045-2257    

DOI:10.1002/gcc.2870070207

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

年代:1993

数据来源: WILEY

摘要:

AbstractCytogenetic analysis has been carried out on 8 early passage cell lines derived from 8 untreated human oral squamous cell carcinomas. Clonal aberrations were detected in the karyotypes of each cell line. A high frequency of breakpoints were noted on chromosomes 1, 7, 8, 9, 11, and X. An isochromosome 8 was present in 6 out of 8 cell lines; isochromosome 9 (3 cell lines) and isochromosome 11 (1 cell line) were also found. In 4 out of 8 cell lines the X chromosome harboured breakpoints, a novel finding in oral squamous cell carcinomas. Breakpoints were common on chromosome 1, with 1p12–p13 most frequently involved. Tandem duplication of 11q13–q23, which contains a number of growth regulatory genes, was also noted in 2 cases. We correlate the sites of proto‐oncogenes and other growth control genes with chromosomal breakpoints and suggest that several of these may play a role in the pathogenesis of oral cancer. © 1993 Wiley‐L

ISSN:1045-2257    

DOI:10.1002/gcc.2870070208

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

年代:1993

数据来源: WILEY

摘要:

AbstractTelomeric associations were determined in bone marrow preparations from a patient with B‐cell prolymphocytic leukaemia and a clonal isochromosome of the long arm of chromosome 17. Thirteen associations involved 16 chromosome arms, with preferential involvement of the short arm of chromosome 19 and the long arm of 17. © 1993 Wiley‐Liss,

ISSN:1045-2257    

DOI:10.1002/gcc.2870070209

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe present the cytogenetic findings in a case of a newly described tumor of childhood, intra‐abdominal desmoplastic small round cell tumor (IADSRCT). The karyotype demonstrated a single chromosomal translocation, (11;22)(p13;q12). © 1993 Wiley‐Liss,

ISSN:1045-2257    

DOI:10.1002/gcc.2870070210

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.2870070211

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

年代:1993

数据来源: WILEY