摘要:

AbstractUsing a database comprising 13,266 cytogenetically abnormal neoplasms, the geographic heterogeneity of neoplasia associated chromosomal abnormalities was investigated by comparing the frequencies of characteristic aberrations in consec utive series of patients with the same diagnosis. Significant frequency differences between geographic areas were found for the aberrations +8, i(17q), +19, and an additional Ph1chromosome in chronic myeloid leukemia (CML); ‐5, 5q‐, and +8 in acute nonlymphocytic leukemia (ANLL); t(8;21) in ANLL‐M2; t(15;17) in ANLL‐M3; 5q‐ and ‐7 in myelodysplastic syndromes (MDS); t(9;22) and +21 in acute lymphocytic leukemia (ALL); t(14;18) in follicular lymphoma; ‐8 and ‐22/22q‐ in menin gioma; and structural abnormalities of 12q in pleomorphic adenoma of the salivary glands (PAS). No geographic incidence variation was detected for ‐7 and +21 in ANLL; +8 in MDS; 6q‐ and +8 in ALL; + 12 in chronic lymphocytic leukemia; 6q‐in non‐Hodgkin's lymphoma (NHL); t(8; 14) in Burkitt's lymphoma; t( 11;22) in Swing's sarcoma; i( 12p) in germ cell tumors; I p‐in neuroblastoma; structural abnormalities of 3q, 8q, and 9p in PAS; or 3p‐ in renal cell carcinoma. Intraregional frequency similarities between cytogenetically identical abnormalities in related tumor types were also analyzed. No significant correla tions were found regarding the incidence of 5q‐ in ANLL and MDS, 6q‐ in ALL and NHL, ‐7 in ANLL and MDS, +8 in ANLL and CML, +8 in ANLL and MDS, +8 in ALL and ANLL, or +21 in ALL and ANLL. The findings indicate that some geographic heterogeneity of tumor‐associated aberrations exists both in hematologic neoplasms and in solid tumors. This could be due to genetic factors, although at present no evidence supports this explanation, or to environmental factors, which have been shown to influence the chromosome pattern in some tumor types. It is also possible that both factors are of importance but in different stages of tumorigenesis. Primary and secondary abnormalities may originate through different mechanisms; e.g., environmental factors might be mainly involved in the genesis of primary anomalies, whereas constitutional factors migh

ISSN:1045-2257    

DOI:10.1002/gcc.2870030102

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

年代:1991

数据来源: WILEY

摘要:

AbstractA new strategy for mapping chromosome translocation breakpoints in relation to known genes has been developed. This approach is based on the amplification by the polymerase chain reaction (PCR) of specific target sequences from small numbers of microdissected chromosome fragments. This method has been applied to leukaemia‐associated translocations affecting the q23 region of chromosome I I. In two independent leukaemias, the t(6; 11) translocation was distinguished from the t(9; 11) and t(4; 11) translocations by demonstrating that the former breakpoint on chromosome 11 lay proximal to the CD3D gene while the latter breakpoints lay distal to CD3D. All three translocation breakpoints were found to lie proximal to ETSl and THYl. The data suggest that although these leukaemia‐associated breakpoints on chromosome 11 are cytogenetically identical they may involve disruption of different genes. This approach offers a rapid alternative to mapping by hybridisation of probes either in situ to chromosomes or to somatic cell hybrids containing the appropriate derivative chromoso

ISSN:1045-2257    

DOI:10.1002/gcc.2870030103

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

年代:1991

数据来源: WILEY

摘要:

AbstractSequential cytogenetic studies were performed on a minimum of two and a maximum of nine occasions (mean 3.6) on the peripheral blood leucocytes of 112 patients with B‐CLL. On initial cytogenetic analysis, 58 had a normal karyotype and 64 had a clonal abnormality. Karyotypic evolution occurred in 18 patients (16%). There was no significant difference in the incidence of disease progression between patients with a stable karyotype and those who underwent karyotypic evolution. In only one patient was there a clear association between disease progression, a change in cell morphology and karyotypic evolutio

ISSN:1045-2257    

DOI:10.1002/gcc.2870030104

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

年代:1991

数据来源: WILEY

摘要:

AbstractTwo adenoid cystic carcinomas, one of the nasal cavity, the other a bronchial tumor, were cytogenetically analyzed. The former had a t(6;9)(q21‐22;p13‐21) as the sole karyotypic abnormality. The latter had two related abnormal clones, resulting in the mosaic karyotype 46, XY, t(9;17)(p13;p13)/46, Y, t(X;6)(p22;q23), t(9;17)(p13;p13). The karyotypic profiles of the two cases, the only respiratory tract adenoid cystic carcinomas that have been cytogenetically characterized, differ little from those of previously reported adenoid cystic carcinomas of the major salivary glands, underscoring the fundamental biologic similarity among these tumors even when they develop from different structures and in different anatomical sites and organs. Because in the second case the t(9;17) obviously must have preceded the t(X;6), we conclude that both tumors had rearrangement of 9p13 as the primary cytogenetic change. The data thus add to the evidence that 6q changes are frequent, albeit at least sometimes secondary, aberrations in malignant salivary gland tumors. A subset of adenoid cystic carcinomas instead have rearrangement of 9p as the primary, and presumably pathogenetically essential, abnormal

ISSN:1045-2257    

DOI:10.1002/gcc.2870030105

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

年代:1991

数据来源: WILEY

摘要:

AbstractWe performed molecular cloning and sequencing of the breakpoints of a new chromosomal translocation involving theMYCprotooncogene locus. This secondary t(8; 12)(q24;q22) was associated with a primary t( I I; 14)(q I 3;q32) translocation in a case of B‐cell chronic lymphocytic leukemia (CLL) in blastic transformation. In this leukemia, Northern blot and nuclease analyses SI showed thatMYCwas strongly expressed with initiation of the transcription at both the 5′ and 3′ promoters as observed in Burkitt's lymphomas; no coding change was observed inMYCputative regulatory sequences. The breakpoint on chromosome 8 mapped to the 3′ end of theMYClocus, in a region containing a potential Z‐DNA tract, and where we identified two DNase I hypersensitive sites. A rearrangedMYCgene fragment was cloned and shown to contain chromosome 12 information by Southern blot analysis and by in situ hybridization. A genomic probe subcloned from the isolated region of the chromosome 12 recognized a 1.8 kb transcript in virtually all the tissues tested but a preferential expression of this new gene, which we termedBTGI(for B‐cell translocation gene I) was observed in the CLL cells and in tissues of lymphoid origin. This chromosome 12 coding sequence is conserved in evolution and a transcript of similar size is present in mur

ISSN:1045-2257    

DOI:10.1002/gcc.2870030106

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

年代:1991

数据来源: WILEY

摘要:

AbstractCytogenetic analyses of four consecutive hepatobiastomas revealed near‐diploid stemline karyotypes with relatively simple chromosome aberrations. Cytogenetic abnormalities shared by each tumor included trisomy for all of part of chromosome 2 and trisomy for chromosome 20. In two cases, partial trisomy for chromosome 2 resulted from direct duplication of long arm material with the shortest region of overlap being 2q23‐2q35. In one tumor, each metaphase also contained a variable number of double minute chromosomes found not to derive fromNMYCamplification. Interestingly, trisomy for 2q and trisomy 20 are also characteristic events in pediatric embryonal rhabdomyosarcomas. Furthermore, others have reported loss of heterozygosity for the short arm of chromosome 11 in both hepatoblastoma and childhood embryonal rhabdomyosarcoma, and both these malignant diseases are associated with Beckwith‐Wiedemann syndrome. These cytogenetic and molecular findings suggest a parallel pathway of genetic steps in the initiation and/or progression of tumors of embryonal liver and skeletal m

ISSN:1045-2257    

DOI:10.1002/gcc.2870030107

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe t(4; II )(q21;q23) has been associated with acute lymphocytic leukemia (ALL) especially in infants. The t(4; II) breakpoint on chromosome II is cytogenetically indistinguishable from breakpoints for other leukemia‐associated translations affecting 11q23. The molecular basis of the t(4;lI) is unknown although a number of genes have been mapped to IIq23. TheCD3D, G, andEgenes have been positioned proximal to the IIq23 breakpoint of the 4; II translocation while theTHY IandETSIgenes have been mapped distal to this breakpoint. We report evidence thatCD3Gis within 200 kb of the 4; II breakpoint as observed by pulsed field gel analysis. A rearrangement of theCD3Ggene has been observed in a cell line derived from a patient with the t(4;II) translocation and in a hybrid cell line containing the derivative IIq chromosome derived from this cell line, using the restriction enzymes Sacll andClal. Similar rearrangements usingSacllwere observed in 2 further patients with ALL and the t(4; II) translocation. No rearrangements in the same DNA were observed usingETSI, THY I, andDl IS29and a range of rare cutter restriction enzymes.CD3Gthus provides a tool for the cloning and analysis of the 4; II trasnslocation, and poses a question of its possible involvement at long range with this translocatio

ISSN:1045-2257    

DOI:10.1002/gcc.2870030108

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

年代:1991

数据来源: WILEY

摘要:

AbstractIn situ hybridization, using a biotinylated cDNA probe for the epidermal growth factor receptor(EGFR)gene, indicates that the amplifiedEGFRgenes in the colon tumor cell line, DiFi, are localized in many small double minute chromosomes (dmin) of varying size and visibility. Analysis of the electrophoretic mobility of γ‐irradiated DNA from DiFi by pulsed‐field gel electrophoresis and Southern blot hybridization usingEGFRprobe, indicates that the amplifiedEGFRin DiFi exists in extrachromosomal, covalently closed circular episomes, presumably equivalent to dmin. Two major and one minor species were observed which had estimated sizes of 650, 1,300, and 2,000 kb, respectively. The DiFi cell line appears to represent a unique case of extrachromosomalEGFRgene amplification in human c

ISSN:1045-2257    

DOI:10.1002/gcc.2870030109

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

年代:1991

数据来源: WILEY

摘要:

AbstractTwenty‐six patients who had cytogenetic analyses performed for myeloid malignancies at St. Vincent's Hospital over a 6‐year period were found to have an inversion abnormality of chromosome 16 (25 patients) or t(16; 16) (I patient). Only 16 patients had all the features of M4Eo, while the other 10 patients had diagnoses of M2, M4, M5, RAEB, and RAEB‐T; six of these had abnormal eosinophils. Thus, abnormal eosinophils were present in 22 of 26 patients (85%). Thirteen patients had additional cytogenetic abnormalities at diagnosis, the commonest being +8 in 5, del(7q) in 4, and +21 in 3. Twenty‐three patients received chemotherapy and 20 (87%) achieved complete remission. The median survival of the treated group was 188 weeks with a 61% 2‐year and 45% 5‐year survival. No significant difference in survival was observed between those patients with a diagnosis of M4Eo and those with other diagnoses suggesting that it is the abnormality of chromosome 16 which confers an improved prognosis. Additional cytogenetic abnormalities present at diagnosis did not affect prognosis. CNS relapse was observed in only two patients (8%), thus indicating no increased incidence of this complication. This study supports the premise that a chromosome abnormality involving 16p13 and 16q22 defines a good prognosis subset of myeloid leukemia despite morphological

ISSN:1045-2257    

DOI:10.1002/gcc.2870030110

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

年代:1991

数据来源: WILEY

摘要:

AbstractVon Recklinghausen neurofibromatosis (NFI) is a common autosomal dominant disorder mapped to 17q 11.2 and typically characterized by the occurrence of neural crest‐derived tumors. The gene has recently been cloned using reverse genetics or “positional cloning” approaches. Its function, however, remains unknown. We have performed cytogenetic and molecular analyses on 9 malignant tumors from NFI patients to look for loss of alleles or chromosome rearrangements involving chromosome 17 to test the hypothesis that theNFIgene acts as a recessive “tumor suppressor” gene. Loss of alleles on this chromosome was detected for 3 of 9 malignant tumors. Two peripheral nerve sheath tumors showed allele loss at informative loci on both the long and short arms of chromosome 17. In contrast, a glioblastoma with focal gliosarcoma showed loss of heterozygosity on the short arm of chromosome 17 only, and not at loci on the long arm. One nerve sheath tumor was previously shown by direct sequence analysis to have a point mutation at theTP53locus at 17p 13. These data support a role for the TP53 gene or other genes on the short arm of chromosome 17 in at least some malignancies in NFI. Six other neurofibrosarcomas showed no allele loss at informative loci on chromosome 17. Cytogenetic analysis was performed on 7 tumors, including 2 with allele loss. The two tumors with allele loss showed abnormal karyotypes while all others were normal. Southern blot and pulsed‐field gel analysis using probes within or closely linked to theNFIlocus detected no gross deletions or rearrangements in the tumors studied. These data, together with those of others, show that loss of alleles on chromosome 17 in malignant tumors from NF I patients occurs in some tumors, but is not a consistent finding. Possible explanations for these findings in relation toNFIgene function ar

ISSN:1045-2257    

DOI:10.1002/gcc.2870030111

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

年代:1991

数据来源: WILEY