摘要:

AbstractDNA fingerprints were generated by the oligonucleotide probe (GTG)5from surgically removed tissue and/or primary cell culture of 36 intracranial tumors (31 gliomas, I medulloblastoma, 4 metastatic carcinomas) and compared with the constitutional banding pattern obtained from the peripheral blood leukocytes of each patient. A multitude of somatic changes was detected and found to reflect the chromosome alterations identified by parallel karyotype analysis. Gain and/or loss of bands or significant band intensity shifts could be demonstrated in the fingerprints of more than 80% of the tumors investigated. This included a highly amplified fingerprint fragment in five independent gliomas (four of them had double minutes, dmin) which appeared not individual‐ but tumor‐specific (2.4 kilobases, kb, afterHaell digestion). Rehybridization with the oligonucleotide probes (GT)8and (GATA)4, respectively, revealed additional amplified fingerprint fragments in the tumor DNA of these patients. While a (ca/gt)nfragment (2.6 kb.HaeIII) was also found to be amplified in all five cases, one band detected with (GATA)4( 1.4 kb,HaeIII) represented a unique feature for one of these tumors only. Amplification of the epidermal growth factor receptor (EGFR) gene via Southern blot hybridization was revealed only in those tumors showing the amplified DNA fingerprint fragments as well. Thus in many gliomas the amplification unit harbors two simple repetitive DNA fingerprint loci, (cac/gtg)nand (ca/gt)n, in addition to theEGFRg

ISSN:1045-2257    

DOI:10.1002/gcc.2870030202

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

年代:1991

数据来源: WILEY

摘要:

AbstractIn order to search for small tumor‐specific deletions in 11 p 13 we analysed DNA isolated from 30 fresh Wilms' tumor (WT) samples with pulsed field gel electrophoresis. For these studies we have isolated new probes from the ends of several Nod fragments. Using these and previously described probes from 11 p 13 we first completed and extended the existing map of the 11 p 13 region. The analysis of the tumor material showed that (1) tumor‐specific deletions were very rare: one homozygous deletion out of 30 tumors analysed, (2) hemizygous deletions were not observed in any of the tumors. The homozygous deletion in one patient spans 220 kb and is composed of a tumor‐specific translocation associated with a deletion on one chromosome and a deletion of about 220 kb on the other chromosome at the same site. The WT‐33 Wilms' tumor candidate gene maps to this deleted segment. A small constitutional deletion of 1,300 kb was identified in a patient with WT and genital tract malformations. These results suggest that in the majority of sporadic WT loss of gene function is due to subtle alterations in the gene, e.g., point mutations or very small de

ISSN:1045-2257    

DOI:10.1002/gcc.2870030203

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe development and application of a procedure for interphase cytogenetics on brain tumor material is described. Nuclei isolated from freshly removed brain tumor tissue were investigated for chromosomal aberrations by nonradioactive in situ hybridization with a panel of chromosome‐specific probes. The panel consisted of nine satellite DMA probes specific for the centromeric regions of chromosomes 1, 6, 7, 10, 11, 17, 18, X, and Y. For each probe, the number of hybridization signals per cell was determined in 200 nuclei. It was inferred from the hybridization results that in 11 gliomas (seven astrocytomas grade II‐IV, three oligodendrogliomas, and one ependymoma) the numerical aberrations were gains of chromosomes 1 (once), 7 (twice), 10 (once), 11 (twice), and X (twice); losses of chromosomes 1 (once), 10 (twice), 17 (twice), and Y (once); and complete tetraploidy (once). Among the 18 investigated meningiomas monosomy 18 and trisomy 17 were observed once and twice, respectively. An additional hybridization with a cosmid probe for theBCRgene on 22q 11 indicated monosomy 22q in 11 meningiomas. These results show the value of interphase cytogenetics for the analysis of solid tumors for which it is relatively difficult to obtain sufficient metaphases of good quality for conventional cytogenet

ISSN:1045-2257    

DOI:10.1002/gcc.2870030204

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

年代:1991

数据来源: WILEY

摘要:

AbstractBoth cytogenetic and molecular genetic analyses of the 11 p 15.5 subband suggest it may contain loci important in the genesis of a wide variety of tumors such as rhabdomyosarcomas and Wilms' tumors as well as the congenital tumors associated with the Beckwith‐Wiedemann syndrome. As a first step in further defining the involvement of this chromosomal region in these various maladies, a library was constructed from the specific microdissection of chromosomal fragments representing 11p 15.5‐pter. Of 98 microclones analyzed, 31 identified single copy human DNA sequences, 21 of which mapped to 11 p 15.5 while 10 mapped proximal to theHBBClocus. Five of the 11 p 15.5‐positioned microprobes detected restriction fragment length polymorphisms at their homologous genomic loci for various enzymes. These microprobes are now being utilized in several ways in order to address the underlying basis of the Beckwith‐Wiedemann syndrome and its associated

ISSN:1045-2257    

DOI:10.1002/gcc.2870030205

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

年代:1991

数据来源: WILEY

摘要:

AbstractWe report a new class of molecular lesions in the 5′ region of theBCL2protooncogene when it undergoes a t(14;18) translocation‐associated rearrangement in the major break cluster (MBR) or minor break cluster (MCR) regions. Among 52 tumors assayed forBCL2rearrangements using the MBR, MCR, and 5′ probes, seven (six with MBR and one with MCR translocation breaks) showed aberrant bands in unique enzyme digests of DNA hybridized with the 5′ probe. The aberrant bands in four tumors were inHindIII digests, in two they were inEcoRI digests, while the aberrant band in one was in aBamHI digest. The twoEcoRI bands and two of the fourHindIII bands were of identical sizes. Germline polymorphisms as the source of these bands was ruled out by appropriate control experiments. These results suggest that the bands were derived from point mutations or small deletions in the 5′ region ofBCL2. The significance of this alteration toBCL2function in translocation‐carrying tumors remains to be

ISSN:1045-2257    

DOI:10.1002/gcc.2870030206

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

年代:1991

数据来源: WILEY

摘要:

AbstractCytogenetic and restriction fragment length polymorphism (RFLP) analyses were performed on a mediastinal germ cell tumor comprising distinct teratoma and embryonal rhabdomyosarcoma components in a 31‐year‐old male and a hepatoblastoma in a 2 month‐old male child. Clonal relationship between the teratoma and rhabdomyosarcoma of the germ cell tumor was established by the presence in both of i(12p), the characteristic marker of germ cell tumors. Both the rhabdomyosarcoma component of the mediastinal germ cell tumor and the hepatoblastoma exhibited rearrangements of 2q. These data suggest that malignant differentiation of a teratoma is accompanied by the development of chromosome abnormalities specific for the transformed histology and further suggest that 2q abnormalities may be the common genetic link in the development of the two histologically unrelated tumor types, embryonal rhabdomyosarcoma and hepatobla

ISSN:1045-2257    

DOI:10.1002/gcc.2870030207

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

年代:1991

数据来源: WILEY

摘要:

AbstractFifty‐two primary human salivary gland tumors were analyzed for expression of the p 185ERBB2protein using immunohistochemical and immunoblotting techniques. About 63% (33/52) of the tumors expressed the ERBB2 protein. The highest expression levels were detected among the carcinomas, where 32% of the tumors showed intense membrane staining in 25–100% of the tumor cells. In benign pleomorphic adenomas, the corresponding figure was only 12%. Clinical follow‐up data available for 18 of the 19 patients with carcinomas suggested an association between high ERBB2 protein levels and poor prognosis as measured by recurrence of disease and/or the appearance of metastases. These results indicate thatERBB2activation and overexpression could be an important genetic event with possible prognostic implications in a subset of malignant salivary gland t

ISSN:1045-2257    

DOI:10.1002/gcc.2870030208

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

年代:1991

数据来源: WILEY

摘要:

AbstractCOLO320DM and COLO320HSR are cell lines derived from a human colon carcinoma, Both lines have an amplification of theMYConcogene: COLO320DM in the form of double minute chromosomes, COLO320HSR as a large marker chromosome with homogeneously staining regions. We have used pulsed field gel electrophoresis (PFGE) to analyze undigested DNA from both COLO320 cell lines. Upon blotting and hybridization with aMYCprobe, the autoradiograms showed the existence of discontinuities in the amplified DNA domains. Additional evidence indicating a preferential concentration of DNA breaks in the region containing theMYCamplicons was obtained with the alkaline unwinding technique. We propose that amplicons are connected by hairpin formation or Hoogsteen pairing between free DNA ends.

ISSN:1045-2257    

DOI:10.1002/gcc.2870030209

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

年代:1991

数据来源: WILEY

摘要:

AbstractWe have previously shown that the reciprocal translocation t(6;7) associated with the spontaneous immunocytoma of the Louvain rat (RIC) leads to the juxtaposition ofmycto thelgHcluster. In 10 of 14 tumors investigated the breakpoints on themyccarrying chromosome were clustered in a 1.5 kb region 5′ of the intact gene, proximal to themycpromoters. In this paper we describe the effect of the translocation onmyctranscription in the RIC system. Run‐on analysis showed transcriptional attenuation in the normal ratmycgene, similar to the situation in mice and humans. The attenuation was almost completely abrogated in the three immunocytomas studied. Sequence analysis of two tumors failed to reveal any structural changes within exon I, as found by others in Burkitt's lymphoma. We also show that the transcriptional initiation ofmycmRNA is changed in the RICs. In an established line of rat fibroblasts (Rat‐2), the more distalmycpromoter (P2) is the preferred site of initiation. In RIC, however, only 30% of transcripts were initiated from P2. We found that 40% of the transcripts were initiated from PI and 30% from a novel promoter, designated PI a, located between PI a

ISSN:1045-2257    

DOI:10.1002/gcc.2870030210

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

年代:1991

数据来源: WILEY

摘要:

AbstractCytogenetic analysis of short‐term cultures from six adenocarcinomas of the colon revealed trisomy 7 as a recurrent clonal chromosomal abnormality. In three tumors, +7 was the sole change. In the fourth carcinoma, two aberrant clones with simple numerical aberrations were detected; one with +7 and one with +3. Tumors 5 and 6 both displayed two completely different abnormal clones; one had numerous numerical and structural abnormalities and thus was undoubtedly representative of the cancer parenchyma, and the other had only +7. The karyotypic differences between the coexisting clones in the latter two cases seem to argue against an evolutionary scenario in which the karyotypically more complex clones have evolved from the clones carrying trisomy 7 only. Furthermore, in tumor 6 the metaphases with trisomy 7 were found in colonies of fibroblast‐like cells whereas those with a large number of abnormalities grew in colonies of epithelial‐like cells. The combined results indicate that mitoses with trisomy 7 as the sole chromosomal change do not represent the neoplastic parenchyma of colorectal adenocarci

ISSN:1045-2257    

DOI:10.1002/gcc.2870030211

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

年代:1991

数据来源: WILEY