摘要:

AbstractPeripheral T‐cell lymphoma (PTL), which is characterized by hepatosplenic presentation and the γ/δ T‐cell receptor (TCR) phenotype on the malignant cells, is a rare but distinct subtype of non‐Hodgkin's lymphomas. Little is known about the chromosomal changes in these lymphomas. We report the cytogenetic analysis of three patients who had neoplastic proliferation of T γ/δ cells in the spleen, bone marrow, and liver, but not in lymph nodes or skin. Isochromosome 7q and trisomy 8 were observed in all three patients. Isochromosome 7q as the sole abnormality has been previously reported in one patient with similar clinicopathologic features. It is suggested that i(7q) is a primary, nonrandom chromosomal abnormality in hepatosplenic

ISSN:1045-2257    

DOI:10.1002/gcc.2870120302

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

年代:1995

数据来源: WILEY

摘要:

AbstractIn adults, loss of heterozygosity for DNA on 17p has been shown in high‐grade anaplastic astrocytomas (AAs) and glioblastomas multiforme (GMs), and mutation of theTP53tumor suppressor gene has been reported in all grades of astrocytomas. Little is known, however, about 17p deletion andTP53mutation in juvenile pilocytic astrocytomas (JPAs), the most common low‐grade tumors seen in children. To elucidate the genetic characteristics of pediatric high‐grade astrocytomas and JPAs, we performed restriction fragment length polymorphism analysis with probes derived from 17p andTP53mutational studies in 28 tumor specimens. Telomeric chromosome arm 17p markers 144‐D6 andABRwere lost in 6 (75%) of 8 informative tumors classified as high‐grade (7 AAs, 1 GM) and in 2 (10%) of 20 informative JPAs. Loss of 17p probes centromeric to theTP53gene were also detected in 3 AAs and 5 JPAs. Four of the 6 (66%) JPAs with losses of 17p DNA sequences recurred rapidly despite aggressive therapy, whereas only 5 of the other 14 (36%) recurred. Mutation of theTP53gene was detected by polymerase chain reaction and denaturing gradient gel electrophoresis in only 1 JPA and 1 AA. These tumors were also examined forMDM2gene amplification as an alternate inactivation mechanism forTP53gene function: no instances of alteration were identified. These results suggest that a gene or genes in addition toTP53on 17p may be involved in the etiology or progression of high‐grade astrocytomas and aggressive JPAs in children. Further, molecular genetic studies may be an important supplement to current clinical and radiologic data in predicting the outcome and guiding the therapy of children with aggressive and malignant a

ISSN:1045-2257    

DOI:10.1002/gcc.2870120303

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

年代:1995

数据来源: WILEY

摘要:

AbstractChromosome banding analysis of 97 short‐term cultured primary breast carcinomas revealed clonal aberrations in 79 tumors, whereas 18 were karyotypically normal. In 34 of the 79 tumors with abnormalities, two to eight clones per case were detected; unrelated clones were present in 27 (34%) cases, whereas only related clones were found in seven. These findings indicate that a substantial proportion of breast carcinomas are of polyclonal origin. Altogether eight abnormalities were repeatedly identified both as sole chromosomal anomalies and as part of more complex karyotypes: the structural rearrangements i(1)(q10), der(1;16)(q10;p10), del(1)(q11–12), del(3)(p12–13p14–21), and del(6)(q21–22) and the numerical aberrations +7, +18, and +20. At least one of these changes was found in 41 (52%) of the karyotypically abnormal tumors. They identify a minimum number of cytogenetic subgroups in breast cancer and are likely to represent primary chromosome anomalies in this type of neoplasia. Other candidates for such a role are translocations of 3p12–13 and 4q21 with various partner chromosomes and inversions of chromosome 7, which also were seen repeatedly. Additional chromosomal aberrations that give the impression of occurring nonrandomly in breast carcinomas include structural rearrangements leading to partial monosomies for 1p, 8p, 11p, 11q, 15p, 17p, 19p, and 19q and losses of one copy of chromosomes X, 8, 9, 13, 14, 17, and 22. The latter changes were seen consistently only in complex karyotypes, however, and we therefore interpret them as being secondary anomalies acquired during clona

ISSN:1045-2257    

DOI:10.1002/gcc.2870120304

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

年代:1995

数据来源: WILEY

摘要:

AbstractCytogenetic studies of the pediatric solid tumor alveolar rhabdomyosarcoma have demonstrated the presence of a consistent chromosomal translocation, t(2;13)(q35;q14). We recently identifiedPAX3andFKHRas the genes on chromosomes 2 and 13, respectively, that are juxtaposed by this translocation. As one means of detecting the t(2;13) translocation in clinical specimens, we have developed a fluorescence in situ hybridization (FISH) assay that may be used for both interphase and metaphase cells. Translocation of the 5′ region of theFKHRgene to the derivative chromosome 2, and retention of the 3′ region ofFKHRon the derivative chromosome 13 [(der(13)], were demonstrated in metaphase cells from a rhabdomyosarcoma cell line with a previously identified t(2;13) translocation. A 5′PAX3cosmid probe was shown to localize to 2q35 in normal cells, and to translocate to the der(13) in the rhabdomyosarcoma cell line. In order to detect the der(13) in interphase nuclei, we labeled the 3′FKHRand the 5′PAX3cosmid probes with digoxigenin and biotin, respectively, and used these in a two‐color FISH assay. The presence of the der(13) was visualized as juxtaposed or overlapping red and green signals in metaphase and interphase tumor cells. ThePAX3‐FKHRFISH assay was then applied to a series of cytogenetically characterized pediatric sarcoma cell lines. The presence of the der(13) was demonstrated by FISH in all cases containing a cytogenetically detectable t(2;13). The FISH assay was then applied to a series of 20 embryonal and alveolar rhabdomyosarcoma samples. All 10 of the alveolar rhabdomyosarcoma specimens demonstrated a der(13) with the FISH assay. We did not detect aPAX3‐FKHRfusion in 10 embryonal rhabdomyosarcoma cases. Thus, the two‐color FISH assay is a sensitive and rapid means of identifying the t(2;13) in rhabdomyosarcoma specimens, and it will be a useful adjunct for the diagnosis of pediatric small round cell tumors. The cosmid probes for the 5′ and 3′ regions ofFKHR, as well as the probe forPAX3, will be useful for molecular cytogenetic studies of variant translocations in rhabdomyosarcoma, such as

ISSN:1045-2257    

DOI:10.1002/gcc.2870120305

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 used for the examination of ten cases of myeloid leukemia (eight acute myeloid leukemias and two myelodysplastic syndromes). In five cases, genomic gains or losses were identified, which mapped to chromosomal regions known to be involved in this group of malignancies. In comparison to the results obtained by banding analysis, discrepancies were found in three of the ten cases; in two cases, chromosomal imbalances were not identified by CGH because they were present only in small subclones. In the other case, there were no evaluable metaphase cells for banding analysis; CGH revealed an overrepresentation of chromosome 8, which was confirmed by interphase cytogenetics with a chromosome 8‐specific alphoid probe. All abnormalities revealed by CGH were confirmed by G‐banding or subsequent interphase cytogenetic analysis, which demonstrates the high specificity of the method. Furthermore, in all cases, CGH identified the chromosomal imbalances present in the major clone as detected by banding analysis. The good correlation between CGH and chromosome banding results in myeloid leukemias makes this tumor a good model for the assessment of tools that are developed for automated and quantitative CGH analy

ISSN:1045-2257    

DOI:10.1002/gcc.2870120306

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

年代:1995

数据来源: WILEY

摘要:

AbstractHere we report the case of a 7‐month‐old boy who presented with biphenotypic acute leukemia, but with leukemia cells of B‐cell phenotype present at the time of relapse. Two cell lines were derived from bone marrow specimens obtained at relapse, and immunophenotyping and analysis of antigen receptor gene configuration revealed concordance between the patient's leukemic cells and the cell lines. Cell line PER‐377 shows a new chromosomal abnormality, t(2;13)(p12;q34), a molecular rearrangement at chromosome band 11q23 in the absence of a cytogenetically detectable abnormality of this band, and deletion of the genes

ISSN:1045-2257    

DOI:10.1002/gcc.2870120307

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

年代:1995

数据来源: WILEY

摘要:

AbstractMedullary thyroid carcinoma (MTC) occurs sporadically or as part of the inherited cancer syndrome multiple endocrine neoplasia (MEN) type 2. In MEN 2A, germline missense mutations are found in one of five cysteine codons within exons 10 and 11 in the extracellular domain of theRETprotooncogene. In MEN 2B, germline mutations occur in codon 918 (exon 16) within the catalytic core of the tyrosine kinase domain. To determine ifRETmutations similar to those in MEN 2A and 2B play a role in the pathogenesis of sporadic MTC, we analysed 71 sporadic tumours comprising 68 primary tumours and three cell lines, for mutations inRETexons 10, 11, and 16. We found that 23% of sporadic MTC hadRETcodon 918 mutations, while only 3% had exon 10 mutations, and none had mutations in exon 11. We found no exon 16 mutations in MTC from 14 MEN 2A cases. Thus, exon 10 and 11 mutations, commonly found in familial MTC and MEN 2A, rarely occur in sporadic MTC; somatic mutation ofRETcodon 918 appears to play a role in the tumourigenesis of a significant minority of sporadic MTC but not MEN 2A tumours. In addition to their biological interest, these findings may have some clinical application in determining whether a patient presenting with isolated MTC is truly sporadic or is part of an inherited cancer syndrome.

ISSN:1045-2257    

DOI:10.1002/gcc.2870120308

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

年代:1995

数据来源: WILEY

摘要:

AbstractComparative genomic hybridization (CGH) makes it possible to detect losses and gains of DNA sequences along all chromosomes in a tumor specimen based on the hybridization of differentially labeled tumor and normal DNA to normal human metaphase chromosomes. In this study, CGH analysis was applied to the identification of genomic imbalances in 26 bladder cancers in order to gain information on the genetic events underlying the development and progression of this malignancy. Losses affecting 11p, 11q, 8p, 9, 17p, 3p, and 12q were all seen in more than 20% of the tumors. The minimal common region of loss in each chromosome was identified based on the analysis of overlapping deletions in different tumors. Gains of DNA sequences were most often found at chromosomal regions distinct from the locations of currently known oncogenes. The bands involved in more than 10% of the tumors were 8q21, 13q21‐q34, 1q31, 3q24‐q26, and 1p22. In conclusion, these CGH data highlight several previously unreported genetic alterations in bladder cancer. Further detailed studies of these regions with specific molecular genetic techniques may lead to the identification of tumor suppressor genes and oncogenes that play an important role in bladder tumorigene

ISSN:1045-2257    

DOI:10.1002/gcc.2870120309

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

年代:1995

数据来源: WILEY

摘要:

AbstractPulmonary chondroid hamartomas (PCH) are benign tumors that contain mesenchymal and epithelial components. In this series, we identified clonal chromosome aberrations in mesenchymal cells from 10 of 17 PCH. Chromosome band 12q15 was rearranged most frequently (N = 4), and one case had a t(12;14)(q15;q24) that was identical cytogenetically to the characteristic translocation in uterine leiomyomas. Histologic review revealed diverse mesenchymal populations, including undifferentiated cells, cartilage, adipose tissue, and smooth muscle, in most of the PCH. These findings suggest that PCH result from neoplastic transformation of a primitive mesenchymal cell that differentiates along chondroid, adipose, and smooth muscle pathways.

ISSN:1045-2257    

DOI:10.1002/gcc.2870120310

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

年代:1995

数据来源: WILEY

摘要:

AbstractIn a family with a constitutional translocation t(3;6), the oldest member carrying the translocation had developed multiple nonpapillary renal cell carcinomas (RCCs). The translocation breakpoint was positioned between 3p13 and 3p14.1. This is close to the region in which a t(3;8) breakpoint has been reported in a family with hereditary RCC. We defined the location of the t(3;6) and t(3;8) breakpoints by fluorescence in situ hybridization (FISH) analysis with yeast artificial chromosomes (YACs) from the 3p14–13 region. Both interphase nuclei and metaphase cells from translocation‐carrying members of both families have been used, allowing the definition of flanking YACs for each breakpoint. We could thereby clearly confirm that the breakpoints are different, the t(3;8) breakpoint being most distal. In addition, we have shown that both translocation breakpoints are located distal to the homozygously deleted region in the U2020 lung cancer cell l

ISSN:1045-2257    

DOI:10.1002/gcc.2870120311

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

年代:1995

数据来源: WILEY