RET translocations are seen in which of the following subtypes of thyroid carcinomas [A] Papillary thyroid carcinoma

RET translocations are seen in which of the following subtypes of thyroid carcinomas [A] Papillary thyroid carcinoma

[B] Follicular thyroid carcinoma

[C] Medullary thyroid carcinoma

[D] Both [1] and [3]

Answer = [A] Papillary thyroid carcinoma (Ref: Sternberg’s Diagnostic Surgical Pathology, 5th Edition)

Papillary thyroid carcinoma Medullary thyroid carcinomas

RET translocations ie RET/PTC translocation MEN 2 = Associated with germline RET

product are seen in 20-40% of Papillary thyroid mutations

carcinoma. Nonfamilial (sporadic) medullary thyroid cancers

= RET mutations are seen in 50% cases

Hot shot > You need to remember that Chromosomal rearrangements of RET protoncogene (RET/PTC translocations) are seen in papillary thyroid carcinoma but are not seen in medullary carcinomas. Instead that, RET point mutations are seen in MTC. Genes involved in thyroid Oncogenesis

| Gene ie | TSH Receptor Autonomous follicular Not oncogenic adenoma RET/PTC translocation PTC More with radiation exposure MET PTC >> FTC c-erb-2 PTC Overexpressed in PTC, but oncogene is not overamplifed PAX8-PPARy FTC Presence of this fusion oncoprotein may be used to differentiate follicular adenoma from carcinoma PTEN Benign follicular adenoma ras PTC, FTC, HCC, autonomous Early event in carcinogenesis; may Follicular adenoma be associated with aggressive PTC

Hot Shot >> RET gene

[1] RET = Inactivating (loss of function) mutations in RET = Hirschsprung’s disease. [2] RET = Activating (gain of function) germline mutations in RET = MEN2 syndromes [3] RET = Activating somatic mutations = Sporadic thyroid carcinomas.

[4] RET/PTC translocations = Papillary thyroid carcinoma