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Eng C, Smith DP, Mulligan LM, Healey CS, Zvelebil MJ, Stonehouse TJ, Ponder MA, Jackson CE, Waterfield MD, Ponder BA: A novel point mutation in the tyrosine kinase domain of the RET proto-oncogene in sporadic medullary thyroid carcinoma and in a family with FMTC. Oncogene 1995, 10:509-513.
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Rossel M, Schuffenecker I, Schlumberger M, Bonnardel C, Modigliani E, Gardet P, Navarro J, Luo Y, Romeo G, Lenoir G, Billaud M: Detection of a germline mutation at codon 918 of the RET proto-oncogene in French MEN 2B families. Hum Gener 1995, 95:403-406.
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Santoro M, Carlomagno F, Romano A, Bottaro DP, Dathan NA, Grieco M, Fusco A, Vecchio G, Matoskova B, Kraus MH, Di Fiiore PP: Activation of RET as a dominant transforming gene by germline mutations of MEN 2A and MEN 2B. Science 1995, 267:381-383. Transfection of mutant RET alleles in NIH 3T3 cells caused constitutive activation of the RET kinase and transformation, establishing the oncogenic potential of mutant RET.
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Eng C, Mulligan LM, Healey CS, Houghton C, Frilling A, Raue F, Thomas GA, Ponder BA: Heterogeneous mutation of the RET proto-oncogene in subpopulations of medullary thyroid carcinoma. Cancer Res 1996, 56:2167-2170. Subpopulations of MTC patients (several metastases in a single individual or different regions within a primary MTC) were analyzed for somatic c-ret protooncogene mutations. A mutation at codon 918 was found in at least one tumor cell subpopulation in 80% of sporadic tumors. One of two MEN 2A MTCs involved this mutation in addition to the germline ret mutation. The authors suggest that the codon 918 mutation may arise during tumor progression or that MTC is of polyclonal origin.
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