Centrosomal and mitotic abnormalities in cell lines derived from papillary thyroid cancer harboring specific gene alterations

Maric I;Viaggi S;CARIA, PAOLA;FRAU, DANIELA VIRGINIA;Degan P;VANNI, ROBERTA

2011-01-01

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Abstract

Background: Differentiated thyroid carcinoma offers a good model to investigate the possible correlation between specific gene mutations and chromosome instability. Papillary thyroid neoplasms are characterized by different mutually exclusive genetic alterations, some of which are associated with aneuploidy and aggressive phenotype. Results: We investigated the centrosome status and mitotic abnormalities in three thyroid carcinoma-derived cell lines, each maintaining the specific, biologically relevant gene alteration harbored by the parental tumors: RET/PTC1 rearrangement in TPC1; heterozygous and homozygous BRAFV600E mutation in K1 and in B-CPAP, respectively. BCPAP cells showed a statistically significant (P < 0.01) higher frequency of abnormal mitotic figures compared to TPC1 and K1 cells. Conclusions: Our data indicate that RET/PTC1 oncogenic activity is not related to mitotic chromosome impairment and missegregation whereas, based on the consistent difference in types/frequencies of centrosome and spindle abnormalities observed between K1 and B-CPAP cells, the hetero/homozygous allelic status of BRAFV600E mutation seems to be not irrelevant in respect to chromosomal instability development.