BRAF Mutation in Papillary Thyroid Carcinoma

Abstract

The BRAF gene has been found to be activated by mutation in human cancers, predominantly in malignant melanoma. We tested 476 primary tumors, including 214 lung, 126 head and neck, 54 thyroid, 27 bladder, 38 cervical, and 17 prostate cancers, for the BRAF T1796A mutation by polymerase chain reaction (PCR)-restriction enzyme analysis of BRAF exon 15. In 24 (69%) of the 35 papillary thyroid carcinomas examined, we found a missense thymine (T)-->adenine (A) transversion at nucleotide 1796 in the BRAF gene (T1796A). The T1796A mutation was detected in four lung cancers and in six head and neck cancers but not in bladder, cervical, or prostate cancers. Our data suggest that activating BRAF mutations may be an important event in the development of papillary thyroid cancer.

Phase II Efficacy and Pharmacogenomic Study of Selumetinib (AZD6244; ARRY-142886) in Iodine-131 Refractory Papillary Thyroid Carcinoma with or without Follicular Elements

“…This is of great relevance in cancers such as PTC in which the V600E mutation is observed in a median of 52% of cases (37%–73%) for studies reporting data on mutation frequency, and melanoma in which BRAF is mutated in 50% to 60% of advanced cases (14, 33–39). In a recent phase II study of selumetinib in advanced melanoma, a mutated BRAF status conferred a more favorable outcome.…”

Mutational activation of BRAF is not a major event in sporadic childhood papillary thyroid carcinoma

“…[9][10][11][12][13][14][15][16][20][21][22] This variability is due in large part to the heterogeneous nature of tumors encompassed under the designation of papillary thyroid carcinoma, and likely reflects differences in: (1) phenotypic subtypes of papillary thyroid carcinoma, (2) exposure profiles, and (3) other yet undefined population-based characteristics such as patient age. We found, for example, that when the study sample is narrowed to sporadic conventional papillary thyroid carcinomas from adult patients over the age of 60, the prevalence of BRAF mutations approaches 90%.…”

“…1-3). All of the papillary thyroid carcinomas from young patients are shown in the lower three rows (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). For case 3, analysis of both the primary papillary thyroid carcinoma (3P) and its metastatic implant (3M) are shown.…”

“…17 BRAF status of papillary thyroid carcinomas in this young group of patients were compared with 65 adult patients with sporadic conventional papillary thyroid carcinomas previously evaluated using identical detection methodology. 9,10 …”

“…Instead, the most frequent genetic alteration is mutational activation of the BRAF oncogene. [9][10][11][12][13] The RET and BRAF oncogenes represent tandem signaling effectors along the mitogen-activated protein kinase pathway. Activation of RET and BRAF induces constitutive activation of the mitogen-activated protein kinase pathway, but their individual roles in thyroid tumorigenesis are mutually exclusive, not cooperative: A papillary thyroid carcinoma usually harbors a RET/PTC translocation or a BRAF mutation, but not both.…”