摘要:

AbstractWe performed a chromosome analysis of 26 pediatric brain tumors, including 20 primitive neuroectodermal tumors (PNETs), 5 astrocytomas, and I immature teratoma. Specimens were treated with collagenase, placed in overnight or short‐term cultures, and harvested for chromosome analysis. Numerical and/or structural abnormalities were noted in 14 of the 20 PNETs and 4 of the 5 astrocytomas. In 13 PNETs, so‐called medulloblastoma in the cerebellum, an i(17q) was the most frequent structural abnormality, accounting for 30% (4/13). Double minute chromosomes (dmin) were observed in one tumor. Near‐diploidy was demonstrated in three of these PNETs, hyperdiploidy in three, and near‐tetraploidy in three. We could not find any correlation of these cytogenetic findings with the prognosis. In the remaining seven PNETs other than medulloblastoma, the karyotypes of five PNETs demonstrated a variety of numerical and structural abnormalities. As to the astrocytomas, losses of chromosomes 7 and 9 with dmin were observed in two, and structural abnormalities of chromosomes 1 and 17 were also observed in two tumors. In our limited cases, however, we could not find the same chromosome abnormalities that are well known in adult astrocytomas. A congenital immature teratoma showed hyperdiploidy with increased numbers of chromosomes 3, 6, and 12. We conclude that i(17q) is an important chromosome abnormality in medulloblastomas, and that the oncogenesis of pediatric astrocytomas might be different cytogenetically from that of adult astro

ISSN:1045-2257    

DOI:10.1002/gcc.2870110402

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

年代:1994

数据来源: WILEY

摘要:

AbstractAn extended YAC contig has been developed for the 3p14 region containing the hereditary renal carcinoma 3;8 translocation breakpoint and the 3p 14.2 fragile site FRA3B. This region of chromosome 3 has been implicated by chromosomal translocation, deletion, and loss of heterozygosity in the pathogenesis of several malignant diseases. The contig allows accurate positioning of candidate genes, polymorphic markers, and other 3p rearrangements within this region. The contig, spanning approximately 6 Mb of DNA, contains 51 YACs identified by 27 markers, including a subset of CA repeats located in the 3p 14.1–14.2 interval. The order of CA microsatellites, derived from marker content of the YACs, is in agreement with the order previously determined by genetic linkage studies. We find that the protein‐tyrosine phosphatase gamma gene,PTPRG, is located minimally 1 Mb proximal to the t(3;8) breakpoint The more proximal 3p homozygous deletion in the small‐cell lung cancer cell line, U2020, is more than 5 Mb from the site of the 3;8 translocation. This integrated physical and genetic map provides a framework for further investigations of malignant diseases associated with proximal 3p loss. In addition, the positioning of separate 3p 14.2 aphidicolin‐induced breakpoints suggests that FRA3B may represent a region rather than a sing

ISSN:1045-2257    

DOI:10.1002/gcc.2870110403

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe mapping of the naevoid basal cell carcinoma syndrome (NBCCS) and the Ferguson‐Smith syndrome to the same region on chromosome arm 9q has led to speculation that the two conditions may reflect different mutations within the same gene. Loss of heterozygosity of 9q alleles in both familial and sporadic basal cell carcinomas (BCCs) suggests that theNBCCSgene on 9q is acting as a tumour suppressor gene. Although LOH of 9q markers has not been studied in squamous cell neoplasms from patients with the Ferguson‐Smith syndrome, chromosome 9 allele loss has been reported in sporadic squamous cell carcinomas (SCCs) of the skin. In order to characterise further the deleted region on chromosome 9 in BCCs and SCCs of the skin we have examined a series of non‐melanoma skin cancers using a panel of highly informative microsatellite markers. Forty‐four BCCs and 49 SCCs were studied. Loss of heterozygosity of one or more 9q markers was seen in 33 of the 44 BCCs. Only 4 of the 33 BCCs with 9q loss showed loss of 9p markers. Twenty‐two BCCs showed loss of all informative 9q markers. Partial or interstitial 9q deletions were seen in 5 BCCs, and in 3 of these 5 BCCs the breakpoint occurred within the currently defined NBCCS locus. Chromosome 9 loss was seen in 16 of 49 SCCs. In contrast to the low frequency of 9p loss in BCCs, LOH of 9p markers was a common finding in SCCs, occurring in 15 of the 16 SCCs with chromosome 9 loss. In 5 SCCs 9p loss occurred with retention of 9q alleles. The different patterns of chromosome 9 loss in BCCs and SCCs and the failure to detect loss of markers at the Ferguson‐Smith/NBCCS locus in 5 of 7 informative SCCs with partial chromosome 9 losses suggest that the targets for allelic deletion on chromosome 9 in BCCs and SCCs ar

ISSN:1045-2257    

DOI:10.1002/gcc.2870110404

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe t(3;21)(q26;q22) is associated with chronic myelogenous leukemia in blast crisis (CML‐BC), leukemia evolving from (therapy‐related) myelodysplasia, and with leukemia following other hematopoietic proliferate diseases. Molecular cytogenetic analysis and cloning of a few t(3;21) cases indicate that the breakpoints are quite heterogeneous even within a specific clinical phenotype. Interestingly some of the (3;21) breakpoints involve theAMLIgene previously found rearranged in the t(8;21) associated with acute myelogenous leukemia.AMLIis related to the Drosophila generuntand is the human counterpart of the gene for the α subunit of the nuclear polyoma enhancer binding protein (PEBP2) also known as the core binding factor (CBF). In the t(3;21)AMLIwas found rearranged withEAP, a gene on chromosome 3 encoding a small ribosomal protein, as well as withEVII, another gene on chromosome 3. Here we report our study of six cases of t(3;21). By using fluorescence in situ hybridization (FISH) analysis andAMLIprobes we could conclude that at least in two CML‐BC cases the breakpoint occurred in theAMLIintron that is disrupted by the t(8;21). AnAMLI/EAPfusion transcript, different from the one described in a therapy‐related myelodysplasia, was detected in both CML‐BC cases. This transcript is expected to result in a predicted protein containing theAMLInuclear binding domain with an attached stretch of 17 amino acids unrelated to the EAP small ribosomal protein. In the other t(3;21) patients we could not detect anAMLI/EAPtranscript or anAMLI/EVIItranscript. This result suggests heterogeneity of the t(3;21) at the molecular level. TheAMLIchimeric transcripts identified so far, both in the t(3;21) and in the t(8;21), diverge from the normal transcripts either after exon 5 or exon 6. Here we show that in normalAMLItranscripts different splicing events are seen to occur afterAMLIexon 5 as well

ISSN:1045-2257    

DOI:10.1002/gcc.2870110405

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

年代:1994

数据来源: WILEY

摘要:

AbstractMicrocell hybrid lines of A9 mouse fibrosarcoma containing complete or partially deleted human chromosomes 3 (chr. 3) were inoculated into SCID mice. Cell lines derived from the tumors were examined by fluorescent in situ hybridization for the status of the transferred human chromosome and by PCR for marker loss. The SCID tumors arising after the inoculation of 105cells were passaged serially in vivo and regularly showed loss of four markers; D3S1029 (3p21.3–21.2),AP20R(3p22–21.3.)D3S32(3p21.3‐p21.2), andTHRB(3p24). This regularly deleted region is bordered by markersGNA12(3p21.1‐p21.3) andVHL(3p25) that were maintained in a fraction of tumors. Fragments derived from the long arm of chromosome 3 and corresponding markers in the 3q26‐q28 region were retained in all tumors. Our findings may be related to the postulated presence of tumor suppressor genes in the 3p24‐p21 region as indicated by the frequent deletion of this region in renal and small cell lung carcinomas and other solid tumors. The technically cumbersome identification of suppressor genes may be supplemented by an “elimination test” based on analo

ISSN:1045-2257    

DOI:10.1002/gcc.2870110406

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

年代:1994

数据来源: WILEY

摘要:

AbstractIn B‐cell malignancies, the t(11;14)(q13;q32) at the 11q13BCLIlocus is characterized by a scattering of breakpoint sites along a 100 kb genomic region, between theBCLImajor translocation cluster (MTC) and thePRADI(also termedcyclin DIorCCNDI) gene. Recently, the 11q13 breakpoint region was extended on both sides, centromeric to the MTC and telomeric toPRADI.We report here the molecular cloning of a new t(11;14) breakpoint site, 20 kb centromeric to the MTC, from a patient with prolymphocytic leukemia. We subcloned a non‐repetitive DNA fragment near the breakpoint and mapped this new 11q13 probe (pHOIIc) relative to already identified breakpoint sites, using long‐ and short‐range physical mapping within theBCLIlocus. Rearrangements in theBCLIlocus are associated with deregulation of thePRADIgene, which is often overexpressed, particularly in mantle‐cell malignancies. The detectable but weakPRADIexpression in the case we present suggests that this breakpoint centromeric to the MTC still lies inside theBCLIlocus boundaries. We think that attention should be focused on this region centromeric to theBCLI‐MTC, where the investigation of previously unidentified translocations may increase understanding of thePRADIgene deregulation in t(11;14) associated

ISSN:1045-2257    

DOI:10.1002/gcc.2870110407

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

年代:1994

数据来源: WILEY

摘要:

AbstractIt has been shown that the geneERGin 21q22 is rearranged in the the t(16;21)(p11;q22) associated with acute myeloid leukemia (AML).ERGis a member of theETSgene family and is fused withEWSin a subset of Ewing's sarcomas.EWSin 22q12 has a very high homology withFUS(also calledTLS) in 16p11; the latter gene is rearranged in the t(12;16)(q13;p11) that characterizes myxoid liposarcoma. To investigate whetherFUSis involved in the t(16;21) of AML, we used the Southern blot technique and polymerase chain reaction (PCR) to examine the bone marrow of a 3‐year‐old boy with a t(16;21)(p11;q22)‐positive AML. Hybridization of Southern blot filters containing digested DNA with probes forFUSandERGshowed both germline and aberrant fragments. Using specific primers for the 5′ part ofFUSand the 3′ part ofERG, we amplified a 4.4 kb genomicFUS/ERGDNA fragment from the leukemic sample. In a second PCR experiment, in which we used primers upstream of the 5′ part ofERGand downstream of the 3′ part ofFUS, a 5.6 kb fragment was amplified. Blotting and hybridization with specific probes forFUSandERGrevealed that the amplified fragments consisted ofFUS/ERGandERG/FUShybrid DNA. Both PCR fragments, when used as probes, detected germlineERGandFUSas well as aberrant fragments on Southern blot filters. The results suggest that the t(16;21) in AML leads to rearrangement and fusion of theFUSandERGgenes. This is the first example in which two genes, each known to recombine with other genes in different solid tumor types (FUSin myxoid liposarcoma andERGin Ewing's sarcoma), are fused in a hematolog

ISSN:1045-2257    

DOI:10.1002/gcc.2870110408

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

年代:1994

数据来源: WILEY

摘要:

AbstractUterine leiomyoma is the most common tumor of smooth muscle cell origin and is often associated with the recurrent balanced translocation t(12;14)(q13‐15;q24). As an initial step toward finding the gene or genes that are interrupted by the translocation breakpoint, a somatic cell hybrid carrying the derivative 14 as the single t(12;14) translocated chromosome was constructed from a leiomyoma cell line with this translocation. Sequence tagged sites (STS) whose locations on the genetic map of chromosome 14 were known were used to map the breakpoint in the translocated chromosomes. The results of this analysis place the translocation breakpoint on the long arm of chromosome 14 between the proximal markerSPTBand the distal marker D14S77, narrowing the chromosomal translocation breakpoint to a region of approximately 7 cM. The identification of flanking markers on chromosome 14 lays the foundation for efforts to clone the breakpoint and to identify the genes involved in the formation of leiomyom

ISSN:1045-2257    

DOI:10.1002/gcc.2870110409

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

年代:1994

数据来源: WILEY

摘要:

AbstractKaryotypic data on choroid plexus papillomas are scarce and, to date, have revealed no consistent aberrations. We karyotyped a choroid plexus papilloma which was characterized by a stemline of 52,XX, + 7, + 11, + 12, + 12, + 15, + 18. Additional copies of chromosomes 16, 17, and 20 were also observed in a significant proportion of the metaphase cells analyzed. Based upon this index case, we retrospectively analyzed eight additional choroid plexus papillomas by fluorescence in situ hybridization by using pericentromeric probes to chromosomes 7, 11, 12, 15, 16, 17, 18, and 20. Extra hybridization signals were observed in five of the eight cases examined. All five cases had extra signals with the chromosome 7 probe, four cases had extra signals with the chromosome 12 probe, and three cases had extra signals with the chromosome 15, 17, and 18 probes. The overall DNA content of these same cases (as determined by image analysis) suggests that gains of additional chromosomes other than those examined may be present.

ISSN:1045-2257    

DOI:10.1002/gcc.2870110410

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

年代:1994

数据来源: WILEY

摘要:

AbstractCytogenetic analysis of short‐term cultures from a case of monostotic fibrous dysplasia in a 14‐year‐old girl revealed multiple clonal structural rearrangements with evidence of clonal evolution. The karyotype was 46,XX,del(3)(q27),add(10)(q22), add(12)(p13)/46,idem,t(3;8)(p21;q13),add(10)(q26),der(15)del(15)(q15q22)ins(15;?)(q15;?)/46,idem,‐X, + 2,t(3;8),add(10),der(15). The finding of clonal structural aberrations suggests that fibrous dysplasia is a neoplastic lesion which develops as the result of somatic mu

ISSN:1045-2257    

DOI:10.1002/gcc.2870110411

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

年代:1994

数据来源: WILEY