Germline and somatic mutations in an oncogene: RET mutations in inherited medullary thyroid carcinoma

Debbie J. Marsh, Scott D. Andrew, Charis Eng, Diana L. Learoyd, Amanda G. Capes, Ruth Pojer, Ann Louise Richardson, Carol Houghton, Lois M. Mulligan, Bruce A.J. Ponder, Bruce G. Robinson

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)


Inherited cancer syndromes predispose an individual to the development of specific tumors. Somatic and germline mutations in the same tumor suppressor gene, as described in Knudson's two-mutation model, are well recognized. Inherited mutations in the RET proto-oncogene, which encodes a receptor tyrosine kinase, predispose individuals to the multiple endocrine neoplasia type 2 (MEN 2) cancer syndromes. The major component tumor of these syndromes is medullary thyroid carcinoma (MTC). To date, somatic mutations in RET have not been identified in tumors from individuals with MEN 2, although they have been well documented in sporadic MEN 2-related tumors. We have identified, among 16 MEN 2 cases with well-defined RET germline mutations, a somatic missense mutation at codon 918 of RET in 3 of 15 MTCs and in a sample with hyperplastic C-cells (the presumed precursor to hereditary MTC). We suggest that the presence of a somatic mutation, in addition to the preexisting germline mutation in hereditary MTCs, may contribute to tumorigenesis in vivo.

Original languageEnglish
Pages (from-to)1241-1243
Number of pages3
JournalCancer Research
Issue number6
Publication statusPublished - 15 Mar 1996


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