Mutational Profile of Papillary Thyroid Carcinoma in an Endemic Goiter Region of North India

Abstract

Introduction: Mitogen activated protein kinase (MAPK) pathway is regularly altered in papillary thyroid carcinomas (PTCs). Serine/threonine-protein kinase B-Raf (BRAF) V600E mutations were observed very frequently in PTC along with less frequent rat sarcoma (RAS) and rearranged during transfection (RET) gene, also known as RET/PTC translocation. The present study aimed to analyze the mutational profile of PTCs from an endemic Goiter area of North India.

Methodology: Tissues from 109 PTC patients were used to isolate DNA and RNA. BRAF V600E was detected by restriction fragment length polymorphism-polymerase chain reaction (PCR). RAS mutations were screened by using Sanger's sequencing method. RET/PTC rearrangements were analyzed by real-time PCR.

Results: BRAF V600E mutation was detected in 51.38% (56/109) of PTCs, whereas RAS mutations were less frequent. No RET/PTC rearrangements were observed. BRAF V600E was found to be associated with the aggressive clinicopathological features such as lymph node metastasis, distant metastasis, higher tumor-node-metastasis stages, and high-risk groups.

Conclusion: The prevalence of BRAF V600E is high in patients from Indian Subcontinent and found to be associated with aggressive features of PTC. Concomitant mutations of BRAF V600E and RAS mutations impart more aggressiveness to PTCs.

Keywords: BRAF V600E; RAS mutations; papillary thyroid carcinoma.

Figure 1

(a) Representative AGE image of polymerase chain reaction product of BRAF gene (b) polymerase chain reaction-restriction fragment length polymorphism of the wild-type and mutant heterozygous BRAF gene. (c) The sequencing result shows a mixture of T and A at the 1799 site

Figure 2

Results of N RAS (a) N RAS Q61K mutation (b) N RAS Q61R mutation