The transcription coactivator HTIF1 and a related protein are fused to theRET receptor tyrosine kinase in childhood papillary thyroid carcinomas

Children exposed to radioactive iodine as a consequence of the Chernobyl re actor accident ha ce an increased risk of papillary thyroid carcinomas (PTC ), The predominant molecular lesions in these tumors are rearrangements of the RET receptor tyrosine kinase (tk), Here me report on two novel types of RET rearrangement, PTC6 and 7, and describe the fusion products and the re t fused gene (rfg) proteins, Like the other rfg proteins identified so far they are ubiquitously expressed, not membrane-bound and contain coiled coil domains required for constitutive activation of the ret tk domain. In the PTC6 rearrangement the ret tk domain is fused to the aminoterminal part of the human transcription intermediary factor htif 1, In the PTC7 rearrangeme nt the ret tk domain is fused to a novel protein that is strongly related t o htif1, Like htif1 it contains a RBCC motif (ring finger, B boxes, coiled coil domain) located in the aminoterminal part and a phd finger and a bromo domain in the carboxyterminal part. Htif1 and related proteins are transcri ption coactivators for nuclear receptors, thus participating in controlling cellular development, differentiation and homeostasis, This is the first r eport on their involvement in human thyroid carcinogenesis.