1,721,068 research outputs found

    Localization of viral transforming sequences within marker chromosomes associated with tumor formation and progression in a murine fibrosarcoma

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    The low-metastatic RSV-transformed fibrosarcoma line B77-3T3 and its metastatic variant AA12, selected in vitro, have been analysed by blot and in situ hybridization with v-src and murine c-myc specific probes in order to detect molecular rearrangements underlying the transition from the low-metastatic to the high-metastatic phenotype. Previous cytogenetic analysis had evidenced that a marker chromosome of the parental tumor line (chromosome A) is replaced in the metastatic counterpart by a new marker chromosome (chromosome B), possibly arisen by duplication of a chromosome A segment, included between two C-positive regions (L. Doneda et al., 1985). In situ hybridization on chromosome spreads of the two related lines with a (3)H-labelled v-src probe showed that src sequences are located within the marker chromosomes A and B, and the percentage of grains over the AA12 marker chromosome is always double that found on the B77-3T3 marker. These signals were considered to identify v-src sequences as they were found to be slightly amplified in the metastatic variant DNA by blot hybridization with the v-src probe. As regards the intrachromosomal location of the signals, most grains were clustered near the heterochromatic bands, suggesting a possible role for heterochromatic sites in tumor formation and evolution. No involvement of the A and B marker chromosomes was shown by in situ hybridization experiments with a c-myc probe. However the dosage of c-myc sequences was also found to be slightly increased in the metastatic variant DNA

    Loss of Y chromosome with retention of Y heterochromatin in a marker chromosome from a human melanoma

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    A single copy of a der15 chromosome (m3) characterized by a C- and distamycin A-Dapi-positive region was observed in the -Y hyperploid karyotype of a primary human melanoma (Me 1402). The heterochromatic region was located pericentromerically, adjacent at one end to the NOR region of chromosome 15, and at the other to an unclassifiable chromosomal piece. We established that the C-positive block in the marker chromosome originated from Y heterochromatin by high-stringency in situ hybridization with a DNA probe for the 2.1 Hae III Y-specific repeat. Loss of the Y chromosome in tumors has been considered to be a secondary event associated with malignant evolution. It is significant that Me 1402 cells, which are highly malignant, lack the Y chromosome, but retain its heterochromatic portion in the rearranged m3 chromosome

    Three-way and two-way rearrangements involving chromosomes 10, 2, 5 and 5, 2 in two marker chromosomes of a human melanoma cell line

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    Two marker chromosomes (mar1 and mar2), provided with two closely spaced heterochromatic bands, were observed in the 14932 cell line established from a human metastatic melanoma. Fluorescence in situ hybridization (FISH) with the alphoid sequence p82H common to all human centromeres showed strong signals over the double C-bands of mar1 and mar2. These were recognized by a chromosome 2-specific alphoid probe, although chromosome in situ suppression (CISS) hybridization with a chromosome 2 library failed to reveal any painting along mar1 and mar2. The centromere of mar1 was identified by a chromosome 10-specific alphoid sequence and the marker chromosome was decorated from pter to a region proximal to the interpolated C-band by a chromosome 10 library. The centromere of mar2 could not be recognized by any chromosome-specific alphoid probe, but the whole mar2 was decorated by a chromosome 5 library. This library also painted the distal q arm of mar1, which was not painted by the chromosome 10 library, as well as a small band proximal to the double C-band. Identification of the two marker chromosomes reveals their common origin and indicates a role for chromosomes 2, 5 and 10 in the genesis and/or progression of the 14932 melanoma. Alteration to the chromosome-specific alphoid sequence in the centromere of mar2 provides evidence for rearrangement of constitutive heterochromatin alphoid sequences in human tumours

    A rare chromosome 5 heterochromatic variant derived from insertion of 9qh satellite 3 sequences

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    A rare chromosome 5 heterochromatic variant not linked to any clinical sign was identified in a three-generation family. After performing conventional cytogenetics characterization, fluorescence in situ hybridization of D9Z1 indicated that the unusually large qh region of chromosome 5 originated from 9qh, whereas the centromere of the variant chromosome was 5-specific as demonstrated by primed in situ DNA labelling. FISH of probes targeting satellite 3 and beta-satellite sequences of 9qh showed that only satellite 3 sequences were present in the variant 5qh region

    High spontaneous chromosomal damage in lymphocytes from patients with hereditary megaduodenum

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    Chromosomal aberration and micronucleus assays were used to investigate the extent of cytogenetic damage in peripheral blood lymphocytes from four patients in two unrelated families with hereditary megaduodenum. The frequencies of total chromosomal aberrations, which significantly correlated with those of micronuclei, were higher in the patients than in sex- and age-matched controls, with no overlapping between the two groups. The considerable chromosomal fragility in patients with hereditary megaduodenum may be a genotypic marker for preclinical diagnosis predictive of increased cancer risk
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