A NOVEL DELETION IN THE RET PROTOONCOGENE FOUND IN SPORADIC MEDULLARY-THYROID CARCINOMA

Germ line point mutations in the RET protooncogene have been implicate d in four inherited disorders: multiple endocrine neoplasia 2A (MEN 2A ) and 2B (MEN 2B); familial medullary thyroid carcinoma (FMTC); and Hi rschprung's disease, a congenital lack of enteric plexus neurons. Onco genically activated RET has also been demonstrated in some sporadic me dullary thyroid tumors, which show somatic missense mutations in the s ame regions as those found in MEN 2B. Upon screening archival sporadic MTC tumor tissue by nonradioactive single-strand conformational polym orphism analysis (SSCP), a markedly divergent exon 11 pattern was foun d in an unusually aggressive neoplasm. Sequencing of PCR amplified DNA revealed the deletion of nine bases encompassing a key cysteine codon at position 1831-3, often altered in MEN 2A. Normal thyroid tissue fr om the same patient showed a normal SSCP pattern and sequence for this exon. This novel somatic mutation further implicates the RET proto-on cogene in the development of MTC.