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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The identification of nonrandom chromosomal abnormalities in hematologic and solid tumor malignancies, which can serve as specific diagnostic markers, has permitted the application of cytogenetic techniques to the diagnosis of poorly differentiated carcinomas of unknown primary tumor site. Cytogenetic markers specific for germ cell tumors, neuroepithelial tumors, and lymphoma have now been identified in these patients. In the case of germ cell tumor diagnosis, the finding of a cytogenetic marker specific for germ cell cancer was predictive of responsiveness to cisplatin-based chemotherapy and long-term disease-free survival. DNA hybridization techniques, including quantitative Southern blot analysis and FISH, were also used to establish the diagnosis of germ cell tumor, particularly in the setting in which conventional cytogenetic analysis was unsuccessful. In poorly differentiated tumors in which conventional light microscopic, immunohistochemical, and electron microscopic techniques fail to yield a specific diagnosis, the use of molecular and cytogenetic markers in human malignancy promises to increase diagnostic acuity. These techniques have the potential to give clearer insight into the biology of this heterogeneous group of tumors and assist in directing appropriate therapy to patients who indeed may have a highly treatable disease.
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PMID:Genetic analysis in the diagnosis of neoplasms of unknown primary tumor site. 850 18

Recent molecular cytogenetic analysis of uterine leiomyoma cell lines with chromosomal aberrations of 12q14-q15 have indicated that the chromosome 12 breakpoints cluster in a 445-kb region designated ULCR12 (uterine leiomyoma cluster region of the chromosome 12 breakpoints). Here we report the results of FISH studies of five primary pleomorphic adenomas and six primary lipomas and established cell lines of these tumor types characterized by translocations involving the chromosomal segment 12q13-q15. The results reveal that for nearly all tumors and cell lines analyzed, the chromosome 12 breakpoints map within a 350-kb region included in ULCR12, despite the previous cytogenetic assignment of the breakpoints to different bands of that region. In some cases the primary material and additionally analyzed cell lines allowed an even more precise localization of the breakpoints to less than 100 kb. Furthermore, a previously hidden translocation of ULCR12 in one primary tumor could be detected by FISH.
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PMID:Mapping of the translocation breakpoints of primary pleomorphic adenomas and lipomas within a common region of chromosome 12. 861 84

Neuroblastoma demonstrates various clinical behaviors, ranging from spontaneous regression to rapid progression regardless of the therapy used. To study the possibility that progression occurs in neuroblastoma through the accumulation of genetic aberrations, we analyzed the clonal constitution of the primary tumor and metastatic tumor samples from a stage-4 patient. Using cytofluorometry and FISH analyses, intratumor clonal heterogeneity was revealed. In the initial primary tumor sample, the nuclear DNA content indicated the coexistence of diploid and aneuploid clones, and the copy number of chromosome 1 varied from two to six. The chromosome 1 aneusomy population was composed of MYCN-amplified and 1p-deleted clones, whereas, in the chromosome 1 disomy population, coexistence of MYCN-amplified and non-amplified clones as well as 1p-deleted and 1p-intact clones was revealed. In the primary tumor after chemotherapy, the DNA-diploid component had become predominant, although the coexistence of MYCN-amplified and non-amplified clones could still be demonstrated in poorly- and well-differentiated tumor regions, respectively. This contrasted with the findings in the metastatic tumors, in which either diploid or aneuploid clone with MYCN amplification and 1p deletion dominated completely in each metastatic site. The findings suggest that the aneuploid clones had evolved from a diploid clone with MYCN amplification and a 1p deletion which, in turn, may have evolved from a diploid clone with neither MYCN nor 1p abnormality. This illustrates how various stages of multiple-step tumorigenesis may provide clues to a better understanding of the clinical heterogeneity of neuroblastoma.
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PMID:Human neuroblastoma demonstrating clonal evolution in vivo. 959 33

Specific chromosomal abnormalities of chromosomal region 6p21.3 have been described in subsets of many benign mesenchymal tumors. In the presented study, we investigated a series of 36 such cases by FISH, and Southern blot analyses for HMGIY rearrangements. FISH results revealed that the chromosomal breakpoints of 11 pulmonary chondroid hamartomas (PCHs), 12 endometrial polyps (EPs), one lipoma, and two uterine leiomyomas (ULs) were located within a 80 kb region surrounding the HMGIY gene. In 11 PCHs and one UL the breakpoints were located 3' of HMGIY, and one PCH showed a breakpoint 5' of HMGIY. Southern blot analyses with intra- and extragenic probes were performed of primary tumor material or cell lines from one UL, three PCHs, and five EPs. In none of these cases was an intragenic rearrangement found. Finally, we were able to detect expression of truncated HMGIY transcripts by 3'-RACE PCR. Our data clearly show the role of a further member of the HMGI family in the development of benign mesenchymal tumors. Although most of the breakpoints of the chromosomal translocations involving HMGIY are located outside the gene, aberrant transcripts resembling the structure of those observed in the case of HMGIC have been found. Our molecular investigations thus led to the identification of the molecular mechanism by which rearrangements of either of two closely related genes lead to the development of frequent benign mesenchymal tumors in humans.
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PMID:HMGIY is the target of 6p21.3 rearrangements in various benign mesenchymal tumors. 982 99

Soft tissue sarcomas constitute a heterogeneous group of malignant tumors of mesenchymal origin, the classification of which may present a diagnostic challenge. We present here the cytological, histopathological, immunohistochemical, and cytogenetic findings of an unusual case of a highly aggressive sarcoma. Based on the morphology and the immunohistochemical profile, this primitive tumor and its metastases could not be conclusively classified as any of the defined subtypes of sarcomas, although the findings were suggestive of a variant of rhabdomyosarcoma. Cytogenetic characterization using G-banding, SKY, FISH, and CGH revealed almost identical chromosomal compositions of the primary tumor and the metastasis. The hypertetraploid karyotype was characterized by numerical imbalances as well as by an unbalanced translocation t(1;19)(q12;q13.2), which has not been previously reported.
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PMID:A highly aggressive primitive mesenchymal tumor with a translocation (1;19)(q12;q13.2). 1142 51

Data concerning cytogenetic features of childhood ependymoma are rare. In this article, a gain of 1q was identified as the sole alteration in a primary childhood infratentorial ependymoma by comparative genomic hybridization (CGH). A recurrence of this brain tumor was studied using multiplex-fluorescence in situ hybridization (M-FISH) in addition to CGH and G-banding analysis. In accordance with the primary tumor, a gain of 1q corresponding to an isochromosome 1q was observed indicating an early event in the tumor development. Furthermore, M-FISH classified several other rearranged chromosomes including 6q and 17p that have previously been found to be involved in the development and progression of childhood ependymoma.
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PMID:Isochromosome 1q as an early genetic event in a child with intracranial ependymoma characterized by molecular cytogenetics. 1167 79

Thin section arrays of 20 head and neck squamous cell carcinomas were studied by I-FISH for gains (including amplification) and losses of specific genomic segments. These arrays allow the examination not only of a number of tumor sections but also of the surrounding margins and of inconspicuous control tissue in one experiment. All tumor sections examined significantly differed from the inconspicuous control tissues by containing more or less extensive cell populations with aberrant signal constitutions. In no case, however, did the aberrant population constitute the whole area of the section. Gains of signals were strikingly more frequent than were losses. All tumors showed significant gains of the segments examined, the highest differences between tumor and control sections were found for the segments 9q34 and 8q24, followed by 5p15.3 and 11q13. Amplifications were most frequently found of 11q13: 8 of the 20 tumors showed amplifications in more than 20% of the nuclei, while no nucleus with more than four signals was found in any of the control tissues (control: 0%). Amplifications of the target sequences on chromosomes 8 (14 tumors) and 9 (8 tumors) were observed in low but significant percentages of nuclei, no significant cell population was detected with an amplification of 5p15.3. Fourteen tumors exhibited a significant loss of 13q14, and only 8 tumors a significant loss at any other site. In the tumor margin sections, in most cases, the margins apparently were also affected by the one or the other of the genomic changes of the pertinent primary tumor. Nevertheless, there were, in some cases, also large differences depending on the way of analysis, but also on the specific signal constitution considered. Tumor stages T3 and T4 tended to have higher frequency of nuclei with gains of 5p15.3, 8q24, and 11q13 as compared to T2 tumors and less gains of 9q34 and loss of 13q14. With the exception of 8q24 and 13q14 alterations there was also a trend to higher percentages of aberrant nuclei in the margin of T3-4 tumors vs. T2 tumors.
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PMID:Thin section arrays for I-FISH analysis of chromosome-specific imbalances in squamous cell carcinomas of the head and neck. 1183 79

Structural rearrangements involving chromosome band 2p21 characterize a cytogenetic subgroup of benign thyroid tumors. To narrow down the breakpoints of these aberrations, we established two cell lines from benign thyroid tumors showing translocations involving 2p21. These two cell lines and one additional primary tumor were used for FISH-studies with 18 BAC clones. All breakpoints were mapped to a cluster of about 450 kb.
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PMID:Molecular cytogenetic investigations define a subgroup of thyroid adenomas with 2p21 breakpoints clustered to a region of less than 450 kb. 1206 98

Conventional cytogenetic studies have shown that osteosarcomas (OSs) are often highly aneuploid, with a large number of both structural and numerical chromosomal alterations. To investigate the complexity of OS karyotypes in detail, we applied spectral karyotyping (SKY) to a series of 14 primary OS tumors and four established OS cell lines. A total of 531 rearrangements were identified by SKY, of which 300 breakpoints could be assigned to a specific chromosome band. There was an average of 38.5 breakpoints identified by SKY per primary tumor. Chromosome 20 was involved in a disproportionately high number of structural rearrangements, with 38 different aberrations being detected. Chromosomal rearrangements between chromosomes 20 and 8 were evident in four tumors. FISH analysis using a 20q13 subtelomeric probe identified frequent involvement of 20q in complex structural rearrangements of OS cell lines. Characterization of the structural aberrations of chromosomes 8 and 17 by use of SKY demonstrated frequent duplication or partial gains of chromosome bands 8q23-24 and 17p11-13. Other chromosomes frequently involved in structural alteration were chromosomes 1 (47 rearrangements) and 6 (38 rearrangements). Centromeric rearrangements often involving chromosomes 1, 6, 13, 14, 17, and 20 were present. Four of the 14 primary OS tumors were characterized by nonclonal changes that included both structural and numerical alterations. In summary, OS tumors have a very high frequency of structural and numerical alterations, compounded by gross changes in ploidy. This intrinsic karyotype instability leads to a diversity of rearrangements and the acquisition of composite chromosomal rearrangements, with the highest frequency of alteration leading to gain of 8q23-24 and 17p11-13 and rearrangement of 20q. These findings suggest that specific sequences mapping to these chromosomal regions will likely have a role in the development and progression of OS.
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PMID:Spectral karyotyping identifies recurrent complex rearrangements of chromosomes 8, 17, and 20 in osteosarcomas. 1246 45

Alterations in the surface expression of HLA class I molecules have been described as a strategy of tumors to evade recognition by cytotoxic T cells. We detected complete loss of HLA class I antigen presentation for 2 tumor cell lines from 1 melanoma patient, the first originated from a regional lymph node lesion diagnosed simultaneously with the primary tumor and the second established 8 months later from a metastatic pleural effusion sample. Antigen presentation was not inducible with IFN-gamma but could be restored after transfection of tumor cells with b2m cDNA, indicating a defect in b2m expression. Analysis of the nature of this defect revealed that it originated from at least 2 mutational events affecting both copies of the b2m gene: a microdeletion of 498 bp in one b2m gene, including its entire exon 1, and a macrodeletion involving the entire copy of the second b2m gene. Microsatellite analysis pointed to the macrodeletion by demonstrating LOH for several specific markers on the long arm (q) of chromosome 15. Structural imbalance of 15q was verified by FISH. FISH studies also indicated the coexistence of a structurally abnormal variant of chromosome 15q with 2 apparently entire chromosomes 15q harboring the homozygous b2m microdeletion. Block of b2m expression in tumor cells builds a barrier to immunotherapy of cancer patients, and its early incidence should be of major consideration in the development and design of immunotherapeutic strategies.
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PMID:Complete loss of HLA class I antigen expression on melanoma cells: a result of successive mutational events. 1251 95


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