RET/PCM-1: a novel fusion gene in papillary thyroid carcinoma

The RET proto-oncogene is often activated through somatic rearrangements in papillary thyroid carcinomas (PTCs). Three main rearranged forms of RET ha ve been described: RET/PTC1 and RET/PTC3, which arise from a paracentric in version and RET/PTC2, which originates from a 10:17 translocation. We previ ously developed a dual-color FISH test to detect these RET rearrangements i n interphase nuclei of thyroid lesions. This approach allowed us to detect a novel translocation involving the RET region, which was not detectable by RT-PCR with specific primers for known rearrangements. A combination of RT -PCR and RACE analyses finally led to the identification of the fusion gene , which involves the 5' portion of PCM-I, a gene coding for a centrosomal p rotein with distinct cell cycle distribution, and the RET tyrosine kinase ( TK) domain. FISH analysis confirmed the chromosomal localization of PCM-I o n chromosome 8p21-22, a region commonly deleted in several tumors. Immunohi stochemistry, using an antibody specific for the C-terminal portion of PCM- 1 showed that the protein level is drastically decreased and its subcellula r localization is altered in thyroid tumor tissue with respect to normal th yroid. However, heterozygosity is retained for seven microsatellite markers in the 8p21-22 region, suggesting that the nonrearranged PCM-1 allele is n ot lost and that the translocation is balanced.