Frequent RET rearrangements in thyroid papillary microcarcinoma detected by interphase fluorescence in situ hybridization

Papillary thyroid microcarcinomas (measuring 1 cm or less in diameter) are very common thyroid tumors, which are present in 10% to 35% of post-mortem histopathological examinations of individuals whose death was due to a cause other than thyroid cancer. The molecular basis of this tumor is still poorly understood. Somatic mutations are better characterized in clinically evident papillary thyroid carcinomas (PTCs), the most common involving the proto-oncogene RET, which maps to 10q11.2. Molecular alterations of RET always lead to intra- or interchromosomal rearrangements. In this study we have investigated the status of RET in 21 microcarcinomas, by means of interphase fluorescence in situ hybridization (FISH). RET was rearranged in 52% of microcarcinomas, a statistically significant higher frequency than that found previously in clinically evident PTCs using the same technique. Moreover, interphase FISH allowed us to detect a putative novel type of rearrangement in a microcarcinoma, and we observed trisomies of chromosome 10 and other chromosomes in two adenomas surrounding two of the microcarcinomas. The strikingly high frequency of RET rearrangements in microcarcinomas strongly suggests that RET plays a role in the initiation of thyroid tumorigenesis but does not seem to be necessary for the further progression of the tumor.