Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0178874 (tumor progression)
40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In spite of a well-known relationship between exposure to radiation and increased risk for cancer development, the biological mechanisms involved in radiation-induced carcinogenesis remain poorly documented. Various hypotheses are discussed in this paper. It appears that radiation cannot be directly responsible for the numerous genetic alterations of cancer cells. Most of them occur during tumor progression. Only one or a very limited number of them was induced by radiation many years before tumor growth. This long delay is a major difficulty for experimental research and raises many questions. Recently, it has been shown that a genomic instability occurs after many generations in cells descending from irradiated cells. This instability leads to multiple genetic alterations and, preferentially, affects some chromosome structures, particularly telomeres. This kind of telomeric instability - related to the shortening of telomeric DNA sequences - has also been observed in senescent cells as well as in non-senescent cells from patients predisposed to cancer, and this process may possibly also occur in the progeny of irradiated cells.
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PMID:Radiation-induced carcinogenesis: individual sensitivity and genomic instability. 874 60

To trace the sequence of numerical chromosomal aberrations during tumor progression of colorectal tumors, we studied intratumoral heterogeneity of chromosomal copy number by a combined fluorescence in situ hybridization (FISH) and ploidy analysis. We used six formalin-fixed paraffin-embedded tumors of which the mucosal lesions were preserved. Nuclear suspensions were made from the tumor tissues that were scraped from several small regions in 100 micron thick sections. Copy number of chromosomes 1, 7, 17, and 18 were examined by FISH with centromeric repetitive probes. DNA ploidy was monitored by cytofluorometry, and was correlated to the chromosomal copy number on the smear slides of identical nuclear suspension from each tumor portion. All the tumors examined included the DNA-diploid regions in the mucosa, where cancer cells commonly showed monosomy 18 and/or trisomy 7. These chromosomal changes may be quite common early events before the occurrence of DNA-aneuploidy in the development of colorectal tumors. Three out of the 6 tumors included near-tetraploid (3.6-4.1C) cells in deeper invasive regions. Chromosomal constitution of DNA-aneuploid cells was suggested to derive from that of DNA-diploid cells through ploidy duplication with or without additional loss or gain of chromosomes.
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PMID:Alteration of numerical chromosomal aberrations during progression of colorectal tumors revealed by a combined fluorescence in situ hybridization and DNA ploidy analysis of intratumoral heterogeneity. 883 Jul 25

Loss of chromosome 7 (-7) or deletion of its long arm (7q-) are recurring chromosome abnormalities in myeloid disorders, especially in therapy-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML). The association of -7/7q- with myeloid leukemia suggests that these regions contain a novel tumor suppressor gene(s) whose loss of function contributes to leukemic transformation or tumor progression. Based on chromosome banding analysis, two critical regions have been identified: one in band 7q22 and a second in bands 7q32-q35. We analyzed bone marrow and blood samples from 21 patients with myeloid leukemia (chronic myeloid leukemia, n = 2; de novo MDS, n = 4; de novo AML, n = 13; t-AML, n = 2) that on chromosome banding analysis exhibited deletions (n = 19) or reciprocal translocations (n = 2) of band 7q22 using fluorescence in situ hybridization. As probes, we used Alu-polymerase chain reaction products from 22 yeast artificial chromosome (YAC) clones that span chromosome bands 7q21.1-q32, including representative clones from a panel of YACs recognizing a contiguous genomic DNA fragment of 5 to 6 Mb in band 7q22. In the 19 cases with deletions, we identified two distinct commonly deleted regions: one region within band 7q22 was defined by the two CML cases; the second region encompassed a distal part of band 7q22 and the entire band 7q31 and was defined by the MDS/AML cases. The breakpoint of one of the reciprocal translocations was mapped to 7q21.3, which is centromeric to both of the commonly deleted regions. The breakpoint of the second translocation, which was present in unstimulated bone marrow and phytohemagglutinin-stimulated blood of an MDS patient, was localized to a 400-kb genomic segment in 7q22 within the deletion cluster of the MDS/AML cases. In conclusion, our data show marked heterogeneity of 7q22 deletion and translocation breakpoints in myeloid leukemias, suggesting the existence of more than one pathogenetically relevant gene.
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PMID:Molecular cytogenetic delineation of deletions and translocations involving chromosome band 7q22 in myeloid leukemias. 905 25

Drug-selected intrachromosomal gene amplification by breakage-fusion-bridge (BFB) cycles is well documented in mammalian cells, but factors governing this mechanism are not clear. Here, we show that only some clastogenic drugs induce drug resistance through intrachromosomal amplification. We strictly correlate triggering of BFB cycles to induction of fragile site expression. We demonstrate a dual role for fragile sites in intrachromosomal amplification: a site telomeric to the selected gene is involved in initiation, while a centromeric site defines the size and organization of early amplified units. The positions of fragile sites relative to boundaries of amplicons found in human cancers support the hypothesis that fragile sites play a key role in the amplification of at least some oncogenes during tumor progression.
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PMID:Expression of fragile sites triggers intrachromosomal mammalian gene amplification and sets boundaries to early amplicons. 910 77

Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric DNA onto the ends of chromosomes, thereby preventing the replication-dependent shortening of these ends. Telomerase activity is detected in a wide range of cancers of various tissues, and its expression may be a critical step in tumor progression. The telomeric repeat amplification protocol was used to compare telomerase activity in breast cancers with and without lymph node metastases, as well as in fibroadenomas and normal breast tissue. Expression of telomerase was detected in 22 (79%) of 28 primary breast cancers, which included 16 (73%) of 22 cancers positive and 6 (100%) of 6 cancers negative for axillary lymph node metastases. It was detected in 1 (11%) of 9 fibroadenomas but was negative in 13 normal breast tissues. There was no statistical difference in expression of telomerase between axillary node-negative primary breast cancers and similar tumors with nodal metastasis (P = .289). Further, no statistical association was found between telomerase activity and tumor size (P = .679) or hormonal status (P = .178). The difference in telomerase activity among breast cancers vs fibroadenomas and normal breast tissues, however, was statistically significant (P < .001). Although normal breast tissue does not express telomerase, both node-positive and node-negative breast cancers express telomerase. The possible significance of telomerase expression in fibroadenomas remains open to further investigation.
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PMID:Telomerase expression in human breast cancer with and without lymph node metastases. 912 66

Fluorescence in situ hybridization (FISH) to sections of formalin-fixed paraffin-embedded archival tissues allows the detection of gene or chromosome copy number changes in interphase cell nuclei within the histological context and thus may be of particular interest in tumor pathology. In this report, we describe the application of FISH to thick (15 microns) paraffin sections of 7 primary cutaneous malignant melanomas. A chromosome 7-specific centromeric DNA probe was used to detect numerical aberrations of chromosome 7. By optical sectioning using confocal laser scanning microscopy (CLSM) only complete, uncut interphase cell nuclei were scored. The mean percentage (+/- SEM) of melanoma cell nuclei with three hybridization spots was (20.7 +/- 2.8)%; (6.8 +/- 1.0)% of nuclei showed one spot and (5.0 +/- 1.2)% four or more spots. The frequency distribution of spot numbers among melanoma cell nuclei and normal keratinocyte nuclei was significantly different (chi(2) = 176.8, df = 5, p < 0.001). Trisomy 7 was detected in all 7 cases analyzed, mostly associated with monosomy 7 or polysomy 7. The approach used in our study and the data obtained could be useful for further studies designed to investigate a possible involvement of chromosome 7 in melanocytic tumor progression.
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PMID:Numerical aberrations of chromosome 7 detected in 15 microns paraffin-embedded tissue sections of primary cutaneous melanomas by fluorescence in situ hybridization and confocal laser scanning microscopy. 916 38

Mantle-cell lymphoma comprises 2%-10% of all non-Hodgkin's lymphomas (NHLs). Patients present with generalized disease, and have a poor prognosis. Three different histologic patterns (mantle zone, nodular, and diffuse) and three different cytological variants (classical, blastic, and pleomorphic) have been described. The phenotype (strong surface IgM, CD5+, CD10-, CD23-, cyclin D1+ and B-cell markers+) is remarkably constant. Dependent on the methods used (PCR, Southern blot analysis, and cytogenetics) a t(11;14) can be detected in approximately 35%-66% of cases. Using FISH analysis, possibly almost all cyclin D1-expressing MCLs carry this translocation, indicating that a substantial part of these translocations are missed by conventional methods. This has been confirmed by DNA fiber FISH analysis by which the breakpoints could be accurately mapped over a 220 kb region centromeric of the cyclin D1 gene. Additional genetic abnormalities involve breakpoints and deletion at the 3' end of the cyclin D1 gene, numerical chromosomal aberrations, mutations in p53, and deletions of p16. These may be associated with tumor progression. Owing to the translocation t(11;14), the cyclin D1 gene is activated. At the RNA level, approximately 90% of MCLs show overexpression. This corroborates immunohistochemistry on paraffin tissue sections. Since expression of cyclin D1 in normal lymphoid cells is very low to undetectable, and only hairy-cell leukemia and very few other B-cell lymphomas show expression, immunohistochemistry for cyclin D1 provides an excellent marker for MCL. In hairy-cell leukemia, expression is moderate and cannot be explained by chromosomal translocation.
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PMID:Bcl-1/cyclin D1 in malignant lymphoma. 920 53

Recent reports have indicated that monosomy 3 is a marker of poor prognosis in uveal melanoma. Fluorescence in situ hybridization (FISH) was performed on fresh touch preparations from 17 uveal, and 5 conjunctival melanomas, using the chromosome 3 centromeric probe, D3Z1. Of the 17 uveal melanomas, all of which originated in the choroid, two cases revealed a monosomy of chromosome 3. One of the conjunctival melanomas contained a major clone that was trisomic for chromosome 3, and another conjunctival melanoma contained a tetrasomic population. FISH, using the alpha-satellite probe for chromosome 3 on uveal melanoma imprints, allows one to predict which patients are potentially at a higher risk of relapse. Multiplication, rather than deletion, of copies of chromosome 3 in conjunctival melanomas may be a nonspecific aberration, perhaps indicative of polyploidy, a characteristic of tumor progression.
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PMID:Assessment of chromosome 3 copy number in ocular melanoma using fluorescence in situ hybridization. 930 11

Recently, lineage-specific genetic pathways of tumor progression have been suggested in both oligodendrogliomas and astrocytomas. Aberrations consistently reported in gliomas include chromosomes 1, 7, 10, 17 and 19. Identification of specific genetic damage may have important clinical consequences, because oligodendrogliomas, unlike astrocytomas, are responsive to chemotherapy. Genetic alterations specific for tumor type and tumor progression were investigated in 5 pairs of recurrent astrocytomas and 8 pairs of recurrent oligodendrogliomas by means of interphase in situ hybridization (ISH) to paraffin-embedded, formalin-fixed tissue sections. A set of DNA probes specific for the centromeric regions of chromosomes 1, 7, 10, 17, X and Y was applied. Since LOH studies on oligodendrogliomas have revealed losses in the region of 1p32-1p36, a DNA probe specific for the 1p36.3 locus was included. Hybridization with the 1p36.3 probe revealed loss of 1p in 5 of the 8 oligodendroglioma recurrences, the aberration being present in the primary tumors in 2 cases. In none of the astrocytomas was loss of 1p observed. Numerical aberrations were found in one astrocytoma pair (+7) and in the second biopsy of an oligodendroglioma (+7, -10). Aneuploidy was found by in situ hybridization in 8 of the 13 tumor pairs. Detection of aberrations in the 1p36.3 locus by interphase in situ hybridization to paraffin-embedded, formalin-fixed tumors may become a very useful tool in delineation of oligodendroglial from astrocytic genotypes, directing tumor specific therapy. The technique may be of crucial importance in tumor cases in which histologic criteria of lineage are not obvious.
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PMID:Detection of chromosomal changes by interphase cytogenetics in biopsies of recurrent astrocytomas and oligodendrogliomas. 932 56

Telomerase is a ribonucleoprotein whose activity has been detected in germline cells and in neoplastic and immortal cells. Telomerase compensates the telomere loss arising by the end replication problem by synthesizing telomeric repeats at the 3' end of the eukaryotic chromosomes. Telomerase is reactivated during cancer progression in human and mice. In order to determine whether the telomerase activity can be upregulated in vitro in response to DNA damaging agents, we examined the telomerase activity in five Chinese hamster cell lines following exposure to 5 J/m2 or 40 J/m2 UV-C radiation. All the cell lines tested showed an increase in telomerase activity in the PCR-based telomeric repeat amplification protocol (TRAP) in a dose dependent manner. This increase in telomerase activity correlated well with the number of cells being in the S and G2/M phase after UV exposure. However, in unirradiated control cells, similar levels of telomerase activity were observed in different phases of the cell cycle. Furthermore, telomeric signals were clustered in one or more parts of the disintegrating nuclear particles of the apoptotic cell as detected by fluorescence in situ hybridization (FISH). This is the first study to demonstrate the induction of telomerase activity following exposure to DNA-damaging agents like UV radiation in Chinese hamster cells in vitro.
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PMID:Induction of telomerase activity by UV-irradiation in Chinese hamster cells. 934 10


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