V599E Mutation of the BRAF Oncogene

This is to bring to the attention of the medical community of the University of Iowa that the Molecular Pathology division of the Clinical Laboratories has validated and introduced a new test for the V599E mutation of the BRAF oncogene. This mutation constitutively activates BRAF and results in papillary thyroid carcinomas.

The method used to detect the pathogenic mutation of the BRAF oncogene is by PCR followed by denaturing high pressure liquid chromatography (dHPLC). This method relies on physical separation of DNA homo and heteroduplexes of the denatured and renatured PCR product; the latter only present if the sample contains the mutated allele of BRAF.

Presence of the mutation is consistent with the diagnosis of papillary thyroid carcinoma. Absence of the mutation does not exclude this diagnosis. The analytical sensitivity of the test is 100% based on comparison of the results with DNA sequencing.

Clinical faculty in Surgical Pathology and Cytopathology will be using this test to help clarify difficult cases where papillary thyroid carcinoma is in the differential diagnosis based on morphologic findings.

Questions and comments concerning the test are to be addressed to Peter L. Nagy, M.D., Ph.D. Tel: 353-4594 or by e-mail: peter-nagy@uiowa.edu.

Puxeddu E et al. 2004. BRAF(V599E) mutation is the leading genetic event in adult sporadic papillary thyroid carcinomas. J Clin Endocrinol Metab. 89(5):2414-20