摘要:

AbstractAstrocytomas, including the most malignant form, glioblastoma multiforme, are the most frequent and deadly primary tumors of the human nervous system. Recent molecular genetic analyses of astrocytomas have demonstrated frequent chromosome 17 deletions involving the telomeric region of the short arm ( 17p 12‐pter). This region contains a candidate tumor suppressor gene,TP53, which has recently been implicated in the etiology of a broad array of human cancers. To study the possible role ofTP53in astrocytoma development, 24 randomly chosen human astrocytic tumors were examined for genomicTP53sequence aberrations using primer‐directed DNA amplification in conjunction with direct sequencing. Five of the 11 grade III astrocytomas (glioblastoma multiforme), but only one of seven grade II astrocytomas (anaplastic astrocytoma) and none of either the grade I astrocytomas or oligodendrogliomas demonstrated distinct point mutations involving theTP53gene. These data suggest thatTP53mutations may play a role in astrocytoma development and are predominantly associated with higher grade tum

ISSN:1045-2257    

DOI:10.1002/gcc.2870030502

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

年代:1991

数据来源: WILEY

摘要:

AbstractA series of 105 patients with acute promyelocytic leukemia (APL) has been cytogenetically investigated at the Department of Hematology of the Saint‐Louis Hospital (Paris) between 1977 and 1990. Sixty‐two patients were examined at diagnosis, 32 in relapse, and 11 both at diagnosis and in relapse. The typical t( 15; 17)(q22;q 12) or variants of this translocation were observed in all but four patients. The t(15;17) was the only change in 47 cases at diagnosis and in 21 examined in relapse. The most frequent secondary change was trisomy 8 (17% at diagnosis). More or less complex chromosomal abnormalities in addition to t(15;17) were present in six patients at diagnosis, and in 17 patients in relapse. Rearrangements of 2q35‐q37 and del(11p) were observed only in relapse and may thus be nonrandom secondary changes. Cytogenetic studies performed on 19 patients treated with all‐trans retinoic acid did not indicate that this treatment induces chromosomal abnorm

ISSN:1045-2257    

DOI:10.1002/gcc.2870030503

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

年代:1991

数据来源: WILEY

摘要:

AbstractCytogenetic study of five biphasic and five monophasic synovial sarcomas revealed the specific abnormality t(X; 18) (p 11;q 11 ) in eight cases and t(X;15;18) (p11;q15;q111) and t(X;7) (q11–12;q32) in one case each. Additional, secondary aberrations were present in eight of these tumors. By combining our data with information on previously published cytogenetically abnormal synovial sarcomas, we were able to evaluate 32 tumor samples from 29 patients. The modal chromosome number was pseudodiploid or near diploid in 26 of the 32 tumors. A t(X; 18) was present in 21 of 29 cases (72%). Complex translocations involving chromosomes X and 18 and another autosome were present in five cases, and one displayed a t(5; 18). There was no visible rearrangement of chromosome bands Xp 11 or 18q 11 in only 2 of the 32 synovial sarcomas. Half of the primary tumors (6 of 12) had the X; 18‐translocation as the sole abnormality. Of the remaining 20 specimens from recurrent or metastatic tumors (in three cases two tumors could be analyzed), only one had t(X;18) as the sole change. The secondary aberrations in cases exhibiting clonal evolution were also generally more extensive in the metastatic and recurrent than in the primary sarcomas (five additional aberrations per case, compared with two). Chromosomes 1 and 12 were the chromosomes most frequently (one fourth of the cases) involved in additional structural changes, but with several different breakpoints. No differences were identified between the karyotypic profiles of monophasic and biphasic synovial sarco

ISSN:1045-2257    

DOI:10.1002/gcc.2870030504

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

年代:1991

数据来源: WILEY

摘要:

AbstractRestriction fragment length polymorphism (RFLP) analysis for allelic losses on the chromosome arm 3p were performed on independent carcinomas produced in athymic nude mice after transformation in vitro of a pseudodiploid clonal SV40‐immortalized human uroepithelial cell line (SV‐HUC). We analyzed ten primary carcinomas with heterogeneous phenotypes for deletions on 3p by using three informative probes, D3S30, D3S2, and D3F15S2, which map to the 3p11‐p14, 3p21.1, and 3p21 regions, respectively. Five of the ten primary cancers showed reduction to homozygosity with at least one of the probes, and all five cancers were high‐grade and poorly differentiated. We also analyzed six carcinomas that arose after progression of low‐grade cancers, either spontaneously or after exposure to a human bladder carcinogen, to higher grades (progressed carcinomas). Four of the six exhibited 3p allelic loss. No preferential loss of a specific 3p allele was observed in any of the carcinomas. In addition, whereas most of the carcinomas showed allelic loss for all three of the probes, indicating a large‐scale deletion, several of the carcinomas exhibited losses for only one or two of the probes, thus making it possible, along with the cytogenetic data, to define the least common region of deletion to 3p13→p14.2. These results support the hypothesis that nonrandom loss of a gene or genes on 3p leads to the development of cancer. Furthermore, these findings associate deletion of a putative 3p13→p14.2 tumor suppressor gene region with the development of high‐grade uroepit

ISSN:1045-2257    

DOI:10.1002/gcc.2870030505

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

年代:1991

数据来源: WILEY

摘要:

AbstractWe report a higher frequency of loss of heterozygosity at loci on the short arm of chromosome 3 in human epidermoid lung tumors than in other non‐small cell lung tumors. This observation together with the already known involvement of the retinoids in the development of epidermoid metaplasia and neoplasia, especially in lung tissue, prompted us to investigate by RNAase protection assays the status of expression of a gene that maps on chromosome band 3p24 and codes for the B receptor for retinoic acid (RARB). We show that expression of RARB is detectable in normal lung tissue and in most of the cell lines derived from lung tumors, including the five non‐small cell lines that clearly had a non‐epidermoid phenotype. Strikingly, however, only one of the five epidermoid‐tumor‐derived cell lines studied showed detectable expression of RARB. Of two lines derived from adenosquamous tumors, one had a clear epidermoid differentiation, and this line also did not express RARB. Taken together, our results strongly implicate RARB in the evolution of epidermoid lu

ISSN:1045-2257    

DOI:10.1002/gcc.2870030506

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

年代:1991

数据来源: WILEY

摘要:

AbstractThere is a paucity of informative data on the potentially important role of specific sites of chromosomal instability in oncogenic processes. Chromosome 2 deletions and rearrangements are known to characterise radiation‐induced acute myeloid leukae mia in the mouse. Here we statistically establish a concordance between chromosome 2 breakpoint clusters in these leukaemias and chromosome 2 rearrangements carried at a high in vivo frequency by progeny of irradiated haemopoietic cells. Mechanisms of radiation myeloid leukaemogenesis are discussed with respect to multiple radiation‐sensitive sites encoded on chromosome 2 and the possible influence of genomic imprinting on inductive proces

ISSN:1045-2257    

DOI:10.1002/gcc.2870030507

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

年代:1991

数据来源: WILEY

摘要:

AbstractAcute myeloid leukaemias (AML) arising in irradiated CBA/H mice frequently have breakpoints in the F region of chromosome 2. The closely linked cytokine genes interleukin(IL)‐lα and β map to this region, and the β gene is deregulated in some AMLs. Using pulsed‐fleld gel electrophoresis techniques, we show here that an 800 kb 2F region encodingIL‐lα and β is not obviously rearranged in six leukaemias carrying chromosome 2 abnormalities. However, changes inIL‐Iregion DNA methylation in three leukaemias may be consistent with loss of hypermethylated sequences from one chromosome copy. These possible 2F region losses are discussed in relation to genomic imprinting and its potential role in murine myeloid leu

ISSN:1045-2257    

DOI:10.1002/gcc.2870030508

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe gene for adenomatous polyposis coli has been localized to 5q21–22. We have mapped six probes from this region using isotopic or nonisotopic in situ hybridization. Using tritium‐labeled probes we localized 11227 (D5S37) to 5q 14–15 and ECB27 (D5S98) to 5q21. Following hybridization with biotin‐labeled probes, the positions of signals along the chromosomes were measured as fractional length relative to the length of the chromosome arm from centromere to qter (FLcen‐qter). Ninety‐five percent confidence limits, compared with standard karyotypes, provided the corresponding band localization. By this method we localized C11 p 11 (D5S71) to FLcen‐qter 0.407–0.452 (5q21.1–21.3), ECB27 to FLcen‐qter 0.426–0.473 (5q21.3), YN5.48 (D5S8I) to FLcen‐qter 0.459–0.496 (5q21.3–22.2), and ECBI34 (D5S97) to FLcen‐qter 0.509–0.533 (5q22.3–23.1). ECB220 had three sites of hybridization, a major site at FLcen‐qter 0.460–0.492 (5q21.3–22.1) and minor sites at FLcen‐qter 0.299–0.339 (5q 14.3–15) and FLcen‐qter 0.629–0.691 (5q23.3–31.2). We have shown that the chromosome 5 breakpoint in a t(5;15) translocation from a patient with Gardner's syndrome (GM03314) is between C11 p11 and ECB27. Linkage data are presented suggesting that ECB27 is located on the same side of theAPClocus as 11227. These and published results including data on several constitutional deletions (M, SD, and brothers PW and ND) give a probable order of [cen] ‐ [11227, proximal SD breakpoint]‐ [C111 p11] ‐ [proximal PW/ND, M breakpoint(s), GMO33 14 breakpoint]‐ [ECB27] ‐ [APC] ‐ [YN5.48]‐[distal PW/ND breakpoint] ‐ [ECB134]‐ [distal M breakpoint] ‐ [qter]. The major site of ECB220 appears to be between ECB27 and th

ISSN:1045-2257    

DOI:10.1002/gcc.2870030509

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

年代:1991

数据来源: WILEY

摘要:

AbstractA 39‐year‐old male with follicular non‐Hodgkin's lymphoma was repeatedly studied with respect to DNA rearrangements with the two probes pFL‐1 and pFL‐2, representing two segments of chromosome 18. The oncogene 6CL2, detected by pFL‐1, was as expected translocated to the J region of the immunoglobulin locus. The standard BCL2 translocation was found in three samples, one obtained at diagnosis, one ten months later, and one after 5 years. Another translocation was found with the probe pFL‐2 hybridizing with a region located about 20 kb 3' from BCL2. This latter rearrangement was found only in the first biopsy, which was obtained at the time of diagnosis, but not in the two later samples, when the morphology of the lymphoma was unchanged. No cytotoxic therapy had been given in the interval from diagnosis to disappearance of the latter rearrangement. Thus, one of the observed translocations (pFL‐2) was detected only in the first biopsy, while the other (pFL‐1) was a clonal marker in all three biopsies. The finding suggests that clonal evolution does not necessarily mean cli

ISSN:1045-2257    

DOI:10.1002/gcc.2870030510

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

年代:1991

数据来源: WILEY

摘要:

AbstractChromosomal in situ suppression (CISS) hybridization was used to investigate the distribution of material of chromosomes 1 and 5 present in marker chromosomes of Namalva cells. The Namalva cell line, established from a Burkitt's lymphoma, exhibits a highly variable female karyotype with a large number of marker chromosomes. Libraries from sorted human chromosomes 1 and 5 were used to delineate material of these chromosomes present in the Namalva karyotype. We used the DAB/peroxidase reaction and reflection contrast microscopy for detection of biotinylated hybrid molecules. Identification of chromosomes was achieved by fluorescent R‐banding after CISS hybridization, which allowed the assignment of hybridized regions to the particular marker chromosomes. After CISS hybridization with a chromosome I library, the normal chromosome I was labelled as well as a large marker MI and the long arm of marker M3. Using a chromosome 5 library it could be shown that the distal part of the long arm of one chromosome 5 was translocated to marker M2. The normal chromosome 5 was completely labelled. The present investigation demonstrates the advantage of combining CISS hybridization and banding for the identification of complex, rearranged tumor karyotype

ISSN:1045-2257    

DOI:10.1002/gcc.2870030511

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

年代:1991

数据来源: WILEY