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Titolo:
Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity
Autore:
Gisselsson, D; Pettersson, L; Hoglund, M; Heidenblad, M; Gorunova, L; Wiegant, J; Mertens, F; Dal Cin, P; Mitelman, F; Mandahl, N;
Indirizzi:
Univ Lund Hosp, Dept Clin Genet, SE-22185 Lund, Sweden Univ Lund Hosp Lund Sweden SE-22185 pt Clin Genet, SE-22185 Lund, Sweden Leiden Univ, Med Ctr, Dept Mol Cell Biol, Lab Cytochem & Cytometry, NL-2333 AL Leiden, Netherlands Leiden Univ Leiden Netherlands NL-2333 AL NL-2333 AL Leiden, Netherlands Katholieke Univ Leuven, Ctr Human Genet, B-3000 Louvain, Belgium Katholieke Univ Leuven Louvain Belgium B-3000 t, B-3000 Louvain, Belgium Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA Brigham & Womens Hosp Boston MA USA 02115 pt Pathol, Boston, MA 02115 USA
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 10, volume: 97, anno: 2000,
pagine: 5357 - 5362
SICI:
0027-8424(20000509)97:10<5357:CBECGI>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
IN-SITU HYBRIDIZATION; SOFT-TISSUE TUMORS; RING CHROMOSOMES; CYTOGENETIC ANALYSIS; GENOMIC INSTABILITY; OVARIAN CARCINOMAS; HUMAN CANCERS; DNA-DAMAGE; ABERRATIONS; P53;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Gisselsson, D Univ Lund Hosp, Dept Clin Genet, SE-22185 Lund, Sweden Univ Lund Hosp Lund Sweden SE-22185 SE-22185 Lund, Sweden
Citazione:
D. Gisselsson et al., "Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity", P NAS US, 97(10), 2000, pp. 5357-5362

Abstract

It has long been known that rearrangements of chromosomes through breakage-fusion-bridge (BFB) cycles may cause variability of phenotypic and genetictraits within a cell population. Because intercellular heterogeneity is often found in neoplastic tissues, we investigated the occurrence of BFB events in human solid tumors. Evidence of frequent BFB events was found in malignancies that showed unspecific chromosome aberrations, including ring chromosomes, dicentric chromosomes, and telomeric associations, as well as extensive intratumor heterogeneity in the pattern of structural changes but notin tumors with tumor-specific: aberrations and low variability. Fluorescence in situ hybridization analysis demonstrated that chromosomes participating in anaphase bridge formation were involved in a significantly higher number of structural aberrations than other chromosomes. Tumors with BFB events showed a decreased elimination rate of unstable chromosome aberrations after irradiation compared with normal cells and other tumor cells. This result suggests that a combination of mitotically unstable chromosomes and an elevated tolerance to chromosomal damage leads to constant genomic reorganization in many malignancies, thereby providing a flexible genetic system forclonal evolution and progression.

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Documento generato il 01/12/20 alle ore 01:14:55