Allelic loss of susceptibility loci and the occurrence of BRAF and RAS mutations in patients with familial non-medullary thyroid cancer.

摘要: Objectives Approximately 5% of non-medullary thyroid cancer (NMTC) diagnoses are made against a background familial predisposition and, in such instances, the disease is termed (FNMTC). To date, neither genetic alterations causing FNMTC nor genes predisposing to condition have been described. The objective present study was evaluate loss heterozygosity (LOH) at four known susceptibility loci (fPTC/PRN, NMTC1, MNG1, and TCO1) compare mutation rates RAS/RAF patients with sporadic NMTC. Methods Fourteen FNMTCs from seven families were analyzed terms involvement loci, 63 tumors [FNMTC (29) NMTC (34)] evaluated for occurrence mutations BRAF, H-, N-, K-RAS, using polymerase chain reaction, single-strand conformation polymorphism (PCR-SSCP) analysis, direct sequencing. Results Only five (35.7%) showed LOH three (NMTC1, or TCO1). These allelic losses did not show specific pattern. Four (13.8%) one (2.9%) had H-RAS (codon 12) mutations. Further, BRAF V600E observed 12 (41.4%) 29 (85.3%) NMTCs. Conclusion Four infrequently involved FNMTC. Although further studies needed, findings additionally suggest that somatic activation oncogenes via RAS plays role tumorigenesis. J. Surg. Oncol. 2012; 105:10–14. © 2011 Wiley Periodicals, Inc.