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BRAF V600E Mutation in Papillary Thyroid Carcinoma: Significant Association with Node Metastases and Extra Thyroidal Invasion

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Abstract

B-Raf (BRAF) is the strongest activator in the downstream of MAP kinase signaling. The somatic point mutation of BRAF gene (V600E) is the most common and specific event in papillary thyroid carcinoma (PTC). However, its prevalence is variable among different studies and its association with clinico-pathological features is controversial. This study tests the prevalence of BRAF V600E mutation in thyroid cancer patients in Indian subcontinental population. We analyzed 140 thyroid tumor specimens for BRAF gene mutation at codon 600 using mutant-allele-specific amplification, single-strand conformation polymorphism, Mutector assay, and DNA sequencing of the PCR-amplified exon 15. BRAF mutation at codon 600 was detected in 46 of 86 PTC patients (53.4%) from Indian subcontinental cohort. Frequency of mutation varied across the subtypes of PTCs. BRAF V600E mutation was more common in the conventional PTC (38 out of 62; 61%) than in the follicular variant of PTC (2 out of 17; 11.7%). None of the 8 follicular thyroid adenomas, 14 follicular thyroid carcinomas, 16 medullary thyroid carcinomas, and 16 benign hyperplasia patients showed any exon 15 mutation. We found significant correlation between BRAF mutation status and extra-thyroidal invasion, lymph node metastasis, and tumor stage. However no correlation was observed with gender, age, and tumor size of the patients. Thus our findings suggest that BRAF V600E is a prevalent genetic alteration in adult sporadic PTCs in Indian cohort and it may be responsible for the progression of classic variant of PTC to metastatic and poorly differentiated subtype and likely to have significant impact on its diagnostic and prognostic management.

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Acknowledgment

The authors would like to thank Dr. Giorgio Stassi (Universita Degli Studi Di Palermo, Palermo, Italy) for kindly providing the thyroid cancer cell lines and Dr. K. M. Mohandas (Dean Academics and HOD DDCN, Tata Memorial Hospital, India) for kind suggestions in stratification of tissue samples for analysis.

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Authors and Affiliations

  1. Radiation Medicine Centre, BARC, C/o Tata Memorial Hospital Annexe, Parel, Mumbai, 400012, India

    Avik Chakraborty, Archana Narkar & M. G. R. Rajan

  2. Molecular Biology Division, BARC, Trombay, Mumbai, 400085, India

    Rita Mukhopadhyaya

  3. Department of Pathology, Tata Memorial Hospital, Parel, Mumbai, 400012, India

    Shubhada Kane

  4. Head and Neck Services, Tata Memorial Hospital, Parel, Mumbai, 400012, India

    Anil D’Cruz

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  1. Avik Chakraborty
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Correspondence to Archana Narkar.

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Chakraborty, A., Narkar, A., Mukhopadhyaya, R. et al. BRAF V600E Mutation in Papillary Thyroid Carcinoma: Significant Association with Node Metastases and Extra Thyroidal Invasion. Endocr Pathol 23, 83–93 (2012). https://doi.org/10.1007/s12022-011-9184-5

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