Topic: CLONAL ORIGIN OF MULTIFOCAL PAPILLARY THYROID CANCER Title: The heterogeneous distribution of BRAF mutation supports the independent clonal origin of distinct tumor foci in multifocal papillary thyroid

COMMENT Papillary thyroid carcinoma (PTC) is the most common cancer of the thyroid gland, accounting for ~85-90% of all cases. PTC often presents as a multicentric tumor, with the lesions representing multiple noncontiguous foci of tumor disseminated in one or both lobes. In the literature, the prevalence of multifocality varies widely, with prevalence figures ranging between 18% & 87% of the cases. These cases are characterized (in general) by one ‘dominant’ tumor, and multiple additional smaller foci, often microcarcinomas. One of the features of PTC that has puzzled me during my entire professional life is the fact that even though multifocality seems to be frequent, one rarely observes recurrences in the remaining lobe after removal of the main lesion by hemithyroidectomy. Thyroid carcinogenesis is a multi-step process where normal thyrocytes evolve to become carcinomatous cells. For PTC, the two well-recognized genetic oncogenic steps are “RET rearrangements” and “somatic BRAF point mutations”, found in 20%-40% and 40% respectively of sporadic PTC. BRAF is a member of the