摘要:

AbstractTwelve B‐cell non‐Hodgkin's lymphomas withBCL6/LAZ3rearrangement selected from a series of 30 lymphomas with cyto‐genetically detectable 3qter abnormalities were characterized at the histological, clinical, and cytogenetic levels, including fluorescence in situ hybridization (FISH) analysis, which was performed in all cases but one. A classical t(3;14) and t(3;22) were found in three patients (25%). In the remaining cases, eleven different 3q27 abnormalities were demonstrated and characterized with the use of chromosome painting. Seven of twelve “variant” rearrangements identified in our series affecting 1p32, 1p34, 3p14, 6q23, 12p13, 14q11, and 16p13 have not been reported before. Moreover, involvement of both homologs of chromosome 3 in distinct translocations was detected as an unexpected result in two cases and was confirmed via FISH in a third case. The putative bichromosomal rearrangements of the 3q27 region were evidenced by Southern analysis in one of these cases. In another case, FISH with a cosmid spanning the 3q27 breakpoint region demonstrated the involvement ofBCL6/LAZ3only in one of two t(3q27).In our series, which was selected on cytogenetic and molecular criteria, 50% (6 of 12) of cases withBCL6/LAZ3rearrangement were diagnosed as diffuse, large B‐cell lymphomas (DLCL). Another 33% (4 of 12) of cases were diagnosed as follicular center lymphomas (FL), with t(14;18)/BCL2 rearrangement in all but one case. Furthermore, in three follicular lymphoma cases in which multiple samples were analyzed, the disease showed no evidence of histological progression during a follow‐up period of 3‐14 years. The present data show that rearrangement of BCL6 is not restricted to high‐grade malignancies as was previously suggested but can also occur in low‐grade lymphomas. In addition, the appearance ofBCL6/LAZ3rearrangement in follicular lymphomas is not related to

ISSN:1045-2257    

DOI:10.1002/gcc.2870140102

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

年代:1995

数据来源: WILEY

摘要:

AbstractComparative genomic hybridization (CGH) was recently developed as a tool to survey entire genomes for variations in DNA sequence copy numbers. We have applied this technique to detect and map amplified regions in 54 soft tissue sarcomas. Aberrations were detected by visual analysis of hybridizations or contrast‐enhanced digital images, followed by quantitative digital ratio imaging of the aberrant chromosomes. Several tumors showed increased DNA sequence copy number at 12q14, as expected. However, CGH analysis detected amplification of 12q14 also in some tumors where neitherMDM2norCDK4was amplified, suggesting that another as yet unknown gene(s) may drive amplification of this region in sarcomas. Furthermore, a novel recurring amplicon was detected at 1q21‐q22. DNA amplifications coinciding with this segment were as frequent as those observed for 12q14, indicating that 1q21‐q22‐linked gene(s) may also play an important role in the development and/or progression of human soft tissue s

ISSN:1045-2257    

DOI:10.1002/gcc.2870140103

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

年代:1995

数据来源: WILEY

摘要:

AbstractUsing comparative genomic hybridization (CGH), we have identified and mapped regions of DNA amplification in primary and metastatic osteosarcomas. Samples were obtained from four patients and ten independent xenografts. Sixty‐four percent of the tumors showed increased DNA‐sequence copy numbers, affecting 23 different chromosomal sites. Most of these regions were not previously associated with the development and/or progression of these tumors. Amplicons originating from 1q21–q23, 6p, 8q23‐qter, and 17p11‐p12 were observed most frequently. The 6p and 17p11–p12 amplicons seem to be specific for osteosarcomas, indicating that these regions may harbor genes relevant for the development of t

ISSN:1045-2257    

DOI:10.1002/gcc.2870140104

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe technique of simultaneous fluorescence immunophenotyping and interphase cytogenetics (FICTION) was applied in four cases of centroblastic‐centrocytic (working formulation: follicular) lymphoma. Our aim in this study was to establish whether secondary chromosome aberrations known from a prior cytogenetic analysis were detectable in both κ‐ and λ‐expressing tumor cells from the same lymphoma patient. One of the cases did indeed contain κ‐ and λ‐positive tumor cells with trisomy 8. On the basis of our results, we reflect on the events that take place during early development of centroblastic‐centr

ISSN:1045-2257    

DOI:10.1002/gcc.2870140105

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

年代:1995

数据来源: WILEY

摘要:

AbstractLoss of heterozygosity (LOH) affecting the long arm of chromosome 6 has been found repeatedly in human cancers. Recently, our group reported that del(6)(q21‐22→qter) was the most consistent structural cytogenetic abnormality in gastric carcinomas. To determine more precisely the deleted region, we studied 51 tumors with 9 polymorphic markers on this chromosome arm. LOH of one or more markers was found in 39% of the tumors. LOH at region 6q22.3 was detected in 50% of informative tumors and at 6q26‐q27 in 37% of informative tumors. By comparative analysis of LOH regions, we identified two separate regions of overlapped deletions at 6q, one between 6q16.3‐q21 and 6q22.3‐q23.1, another distal to 6q23‐q24. A comparison of clinicopathologic features of gastric carcinomas with and without LOH at 6q revealed statistically significant or suggestive differences between LOH and young age of the patients and proximal location of the tumors. The two informative early gastric carcinomas both showed LOH at 6q. The occurrence of LOH at 6q was similar in all histological types. We conclude that two distinct regions at 6q appear to be involved in the early stages of gastric car

ISSN:1045-2257    

DOI:10.1002/gcc.2870140106

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

年代:1995

数据来源: WILEY

摘要:

AbstractChromosomal band Ip36 probably harbours several neuroblastoma suppressor genes. A neuroblastoma patient has been described with a constitutional balanced translocation, t(1;17)(p36;q12‐21). Cytogenetically, no loss of chromosomal material was visible. The Ip36 translocation breakpoint could therefore have inactivated one allele of a tumour suppressor gene, thus predisposing the patient to develop neuroblastoma. We localized this breakpoint by pulsed field gel electrophoresis, analysis of yeast artificial chromosomes, and fluorescence in situ hybridization. Here we report that the breakpoint is within a large cluster of small nuclear RNA U1 (RNU1) and some tRNA genes (TRE, TRN) on chromosomal band 1p36. The size of this cluster is over two megabases and it contains many other locally repeated sequences. Polyadenylated transcripts were identified for some of these sequences. In addition, the cluster is the target for integration of an adenovirus 5/SV40 hybrid virus. The translocation breakpoint maps distal of this viral integration site and proximal of marker PN

ISSN:1045-2257    

DOI:10.1002/gcc.2870140107

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

年代:1995

数据来源: WILEY

摘要:

AbstractSeveral human renal cell carcinomas with X;autosome translocations have been reported in recent years. The t(X;1)(p11.2;q21) appears to be a specific primary anomaly, suggesting that tumors with this translocation form a distinct subgroup of RCC. Here we report two new cases, one with a t(X;10)(p11.2;q23), the other with a t(X;1)(p11.2;p34). The common breakpoint in Xp11.2 suggests that they belong to the above‐mentioned subset of RCC. Using FISH in conjunction with X‐specific YAC clones, we demonstrate that the two new cases exhibited distinct breakpoints within Xp1

ISSN:1045-2257    

DOI:10.1002/gcc.2870140108

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

年代:1995

数据来源: WILEY

摘要:

AbstractUterine leiomyomas are benign tumors that arise clonally from smooth muscle cells of the myometrium. Cytogenetic studies of uterine leiomyomas have shown that about 40% have chromosome abnormalities and that deletion of 7q is a common finding. The observations suggest the possible location of a growth‐suppressor gene within the 7q21‐q22 region. Molecular genetic analysis of cytogenetically normal tumors has frequently shown somatic loss of specific tumor suppressor genes detected by loss of heterozygosity in the critical region. To test the hypothesis that chromosome region 7q21‐q22 contains a growth‐suppressor gene involved in the development of leiomyomas, we examined 92 leiomyomas for allelic loss of 7q markers spanning the cytogenetically defined critical region. Forty tumors with cytogenetically defined 7q deletion, 45 tumors without cytogenetically visible 7q deletion, and seven tumors with no cytogenetic information were examined for allelic loss of loci D7S489, D7S440, D7S492, D7S518, D7S471, D7S466, and D7S530. Loss of heterozygosity for one or more of these loci was observed in 23 of 40 (57.5%) of the tumors with deletion of 7q and in 2 of 45 cases without a cytogenetically visible deletion. The tumors with cytogenetic deletion of 7q, but no loss of 7q21‐q22 markers, were mosaics, with only a minority of cells containing the cytogenetic deletion. The critical region of loss is defined by the markers D7S518 and D7S471, each showing loss in approximately 50% of informative cases. These markers define a 10 cM region of 7q21‐q22 that is consistent with the cytogenetically defined smallest region of overlap and exclude loss of theMEToncogene locus andWNT1, the murine mammary tumor‐virus integration site, from the critical region. Our results further define a region that is consistently lost in leiomyomas with cytogenetic deletion of chromosome arm 7q. This region may contain a tumor suppressor gene involved in the development of a subset

ISSN:1045-2257    

DOI:10.1002/gcc.2870140109

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

年代:1995

数据来源: WILEY

摘要:

AbstractCytogenetic analysis of one case of acute myeloid leukemia (AML), one of acute lymphoblastic leukemia (ALL), one of refractory anemia with excess of blasts (RAEB), and one of acute mixed lineage leukemia (AMLL) with unbalanced 7;12 translocations mapped the breakpoints to the centromeres on both chromosomes. The rearrangements were interpreted as the whole‐arm translocations der(7;12)(q10;q10) in the AML and ALL and der(7;12)(p10;q10) in the RAEB and AMLL. However, further analysis by metaphase and/or interphase fluorescence in situ hybridization (FISH) showed centric fusion only in the AML and ALL. In the RAEB and AMLL, centromeric material from chromosome 7 but not from 12 was present in the derivative chromosome. Whereas the t(7;12) resulted in loss of 12p in all four cases, the corresponding chromosome 7 imbalances differed—monosomy for 7q in the RAEB and AMLL and monosomy for 7p in the AML and ALL. Six hematologic neoplasms with unbalanced whole‐arm or near‐centromeric 7;12 translocations and seven dic(7;12) with juxtacentromeric breakpoints have been reported previously: 2 AML, 1 RAEB in transformation, and 10 ALL. All karyotypically informative cases had loss of 12p material. All but one of the cases with combined 7p and 12p deletion were ALL, whereas all cases with 7q and 12p loss showed myeloid differentiation. No particular clinical, morphologic, or immunophenotypic features seem to characterize ALLs with t(7;12). AMLs with an unbalanced t(7;12), often together with 5q deletions, might be associated with previous genotoxic exposure and poor pr

ISSN:1045-2257    

DOI:10.1002/gcc.2870140110

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe human retinoblastoma cell line Y79 has multiple copies of theMYCNgene and the DEAD box geneDDX1. Both genes have been mapped to chromosome band 2p24. A third gene, encoding the α‐subunit of mitochondrial ATP synthase (ATPSA), is also amplified in Y79. Here we report that there are at least four human mitochondrialATPSA‐related genes located on four different chromosomes. TheATPSAgene that is amplified in Y79 originates from chromosome 18. In Y79, the amplified copies of both theATPSAand theMYCNgenes are located on a homogeneously staining region (HSR) at chromosome band

ISSN:1045-2257    

DOI:10.1002/gcc.2870140111

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

年代:1995

数据来源: WILEY