CLONING AND CHARACTERIZATION OF H4 (D10S170), A GENE INVOLVED IN RET REARRANGEMENTS IN-VIVO

H4(D10S170) is a gene which we isolated because of its frequent rearra ngement with the RET proto-oncogene in vivo. Its fusion to RET generat es the RET/PTC1 oncogene, which has been detected in about 20% of huma n thyroid papillary carcinomas. We have cloned and sequenced the cDNA corresponding to the H4(D10S170) gene from a human normal thyroid cDNA library. The nucleotide sequence of the H4(D10S170) 3kb transcript sh ows no significant homology to known genes and contains an open readin g frame (ORF) of 585 amino acids. H4(D10S170) predicted protein has no transmembrane domain and shows extensive regions in the alpha helical conformation, which are 30%.homologous to the alpha-helical domains o f several proteins including tropomyosin, vimentin, keratin and the ta il region of myosin heavy chain. A putative SH3 binding site is presen t at the carboxy terminus, which suggests that H4(D10S170) might be a cytoskeletal protein.