Showing papers on "Chromothripsis published in 2007"

Genomic Instability and DNA Repair

Abstract: There is growing evidence that genomic instability is both an epiphenomenon and a leading cause of cancer. Chromosomal instability in neoplasia (CIN) is the most frequent type of genomic instability in solid tumours. For more than a century, chromosomal rearrangements and aneuploidy in neoplasia have been extensively studied and a vast number of genes and pathways, directly or indirectly implicated in CIN, have been described. Chromosomal abnormalities in cancer generate huge genomic imbalances and tumour heterogeneity. This chapter addresses the role of genes, chromosome structure, and telomere dysfunction in the initiation and perpetuation of CIN. The biological consequences of large chromosomal imbalances are discussed and the long-standing hypotheses for the generation of chromosomal anomalies in neoplasia are re-examined under the context of telomere dysfunction and restoration. Keywords: DNA repair; genomic instability; telomeres; aneuploidy; chromosome anomalies; ALT

Chromosomal rearrangements and their role in spontaneous immortalization and transformation of rat embryo cells in vitro

Abstract: Peculiarities of chromosomal rearrangements were studied in cells of the spontaneously immortalized LRec-1 and LRec-3 lines derived from rat embryo fibroblasts, as well as in LRec-1k clone cells and LRec-1sf line cells with autocrine regulation of proliferation at various cell transformation stages. The lines were obtained from rat embryo fibroblasts by cloning during rapid aging of the cultures. Using the G-banding of chromosomes, it was shown that in the process of transformation, cells of the LRec-1 and LRec-3 lines as well as of LRec-1sf maintained diploidy and specific clonal rearrangements of chromosomes 7 and 19, which were revealed earlier at the immortalization stage. In the LRec-1 cells, new clonal rearrangements of chromosomes 10 and 20 were observed, while rearrangements of chromosomes 1, 2, 11, 15, 18, and 19 were observed in the LRec-1sf cells. In the LRec-3 cells, as well as in cells of the LRec-1k clone, new chromosome rearrangements were absent. Loci involved in chromosomal rearrangements were compared with the genes located in them according to RATMAP data. The role of rearrangements of chromosomes 7 and 19 in the immortalization and malignant transformation of embryo fibroblasts is discussed, as well as the roles of other chromosomes during acquisition of the specific signs of the transformed phenotype by the LRec-1 and LRec-1sf cells.