Molecular Rearrangements in Papillary Thyroid Carcinomas

Papillary thyroid cancer is unusual among epithelial malignancies in that it is associated with a number of chromosomal rearrangements. The most common of these is the Ret oncogene, normally silent in the follicular cell, but which has been shown to be rearranged to the promoter region of a variety of different genes, all of which are constituently expressed in the thyroid follicular cell. It has been suggested that chromosomes in the thyroid cell are arranged within the nucleus in such a way as to predispose the cell to inappropriate fusion in the advent of DNA double-strand breakage. The presence of tumour specific fusion genes, and their transcribed proteins, presents a possible therapeutic target for thyroid cancer, but the relative contribution of the gene rearrangement in the growth and development of the tumour will need careful evaluation before clinical studies could take place.