To study the role of gene alterations in map kinase pathway in pathogenesis of papillary thyroid carcinoma

Abstract

Thyroid cancer is one of the major endocrine tumors. Papillary Thyroid newlineCarcinoma, Medullary Thyroid Carcinoma, Follicular Thyroid Carcinoma and newlineAnaplastic Thyroid Carcinoma are the four major carcinomas. According to the newlineNational Cancer Institute, there are over 56,000 new cases of thyroid cancer in the newlineUS each year, and the majority of those diagnosed are papillary thyroid cancer. newlineTumors are developed due to the mutations in different signaling pathways newlineassociated with cell proliferation and differentiation. MAP kinase pathway and newlinePI3Kinase are common pathways involved and affected in thyroid cancers. It has newlinebecome apparent that thyroid tumors, especially those of the papillary type, newlinefrequently have genetic alterations leading to activation of the MAP Kinase signaling newlinepathway. Since clinico-pathological features of PTC alone could not determine the newlineaggressiveness of PTC, the role of molecular markers like BRAF, RAS mutations, newlineRET/PTC rearrangements, etc. were further studied in recent years. Therefore, we newlinedecided to study the molecular profiling of PTCs in patients from an endemic goiter newlinearea of North India. If initial events of tumor progression can be determined, it can newlinebe utilized in deciding the mode of treatment. Apart from mutations BRAF V600E newlinemutation and its connection with the lowering of iodine expression genes are newlinepreviously studied. Hence, we also focused to explore the role of iodine metabolizing newlinegenes in PTCs. newlineEthical clearance was obtained from the Institutional Ethical Committee newlineof SGPGIMS. Tissue samples were collected and stored in -800C after liquid newlinenitrogen freezing. DNA and RNA from the samples were isolated and measured the newlinequality and quantity by nanodrop. BRAF and RAS gene portions were amplified newlineusing specific primer set and checked on agarose gel electroporosis. BRAF V600E newlinemutation was screened by Restriction Fragment Length Polymorphism PCR and newlineconfirmed by sequencing by using specific primers. RAS mutations were screened newlineby Sanger s sequencing and RET/PTC rearrangements were checked b