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Titolo: Centrosome aberrations and spindle defects in thyroid carcinoma cells harboring specific oncogene activation
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Data di pubblicazione: 2011
Rivista: 
CHROMOSOME RESEARCH  
Abstract: Papillary thyroid carcinoma (PTC) is characterized by different mutually exclusive genetic alterations, some of which are associated with aneuploidy and an aggressive phenotype. Little is known about the relationship between PTC molecular events and the genomic instability of thyroid tumors. PTCs have a number of variants with specific histological and molecular features: approximately 40% of classical PTCs show activation of the BRAF gene (mainly the BRAFV600E mutation), and approximately 20– 30% harbour activation of the RET/PTC oncogene, secondary to inversions or translocations involving the 10q11.2 chromosome band. A number of different PTC-derived cell lines maintain the tumor-specific oncogenic rearrangement (i.e. RET/ PTC or BRAFV600E) representing a valuable tool to study the mechanisms underlying thyroid carcinogenesis. We investigated the centrosome status and mitotic irregularities in two thyroid carcinomaderived cell lines, TPC1 and B-CPAP, each harboring one of the two biologically relevant specific gene alteration, the RET/PTC1 rearrangement and the BRAFV600E mutation, respectively. Our results indicate different degrees of frequency and type of centrosome and mitotic defects in the cell lines. Cells harboring the RET/PTC1 oncogenic activity have a very low mitotic chromosome impairment and missegregation, in keeping with the low frequency of cytogenetic variation reported in RET/PTC-positive carcinoma and the finding of RET/PTC-positive cells in non-malignant thyreocytes. Cells with BRAFV600E mutation showed multipolarity and several mitotic irregularities, such as metaphase chromosome misalignments, ana- Chromosome Res (2011) 19 (Suppl 1):S37–S231 S123 telophase lagging chromosomes, multipolar figures and c-metaphases, indicating a pronounced high instability potential. The different degrees of frequency and type of centrosome and mitotic defects in the cell lines suggest a dissimilar contribution of specific molecular alterations to the chromosomal instability (CIN). Our findings reinforce the concept that the loss of the ability to control centrosome number and function leads to CIN by means of multipolar spindle formation, aneuploidy and disruption of cell polarity. Partially supported by FIRB/RAS/FBS/A.S.I. grants.
Handle: http://hdl.handle.net/11584/100545
Tipologia:1.5 Abstract in rivista

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