Endocrine-related cancer 2017 10 24() pii 10.1530/ERC-17-0288
A near-homozygous genome (NHG) is especially seen in a subset of follicular thyroid of the oncocytic type (FTC-OV). A NHG was also observed in the metabolically relatively quiescent cell lines XTC.UC1, a model for FTC-OV, and in FTC-133, -236 and -238, the latter three derived from one single patient with follicular thyroid cancer. FTC-236 subclones showed subtle whole-chromosome differences indicative of sustained reciprocal mitotic missegregations. Reactive oxygen species (ROS) scavenger experiments reduced the number of chromosomal missegregations in XTC.UC1 and FTC-236 while pCHK2 was down-regulated in these cells. Treatment with Antimycin A increased ROS indicated by enhanced MitoSOX Red and pCHK2 fluorescence in metaphase cells. In a selected set of oncocytic follicular thyroid tumors increasing numbers of whole-chromosome losses were observed towards an aggressive phenotype, but with retention of chromosome 7. Together, ROS activates CHK2 and links to the stepwise loss of whole-chromosomes during tumor progression in these lesions. We postulate that sequential loss of whole-chromosomes is a dominant driver of the oncogenesis of a subset of follicular thyroid tumors.