Chapters authored
Possible Role of Proto-Oncogenes in Colorectal Cancer — A Population Based Study
Part of the book: Colorectal Cancer
Molecular Alterations and Expression Dynamics in the Etiopathogenesis of Thyroid Cancer
Thyroid carcinoma is the most prevalent endocrine malignancy and accounts for 2% of all human cancers. In the past decade, knowledge of genetic alterations of thyroid cancer (TC) has rapidly expanded, which has provided new insights into thyroid cancer etiology and has offered novel diagnostic tools and prognostic markers that enable improved and personalized management of thyroid cancer patients. Alterations in key signaling effectors seem to be the hallmark of distinct forms of thyroid neoplasia. Mutations or rearrangements in genes that encode Mitogen activated protein kinase (MAPK) pathway effectors seem to be required for transformation. Mutations in BRAF were the most recently identified MAPK effector in thyroid cancer. BRAF V600E is the most common alteration in sporadic papillary carcinoma. Three RAS proto-oncogenes (NRAS, HRAS & KRAS) are implicated in human thyroid tumorigenesis. High incidence of thyroid cancer worldwide indicates the importance of studying genetic alterations that lead to its carcinogenesis. BRAF and RAS alterations represent a novel indicator of the progression and aggressiveness of thyroid carcinogenesis. The GSα-adenylyl cyclase-cyclic AMP (cAMP) cascade is effected in thyroid cancer. Promoter hypermethylation of multiple genes especially TSHR has been identified to play a role in thyroid cancers, in particular showing a close association with BRAF mutational status. So, the main aim of the study was to elucidate the involvement of BRAF and RAS gene mutations along with BRAF expression and thyroid-stimulating hormone receptor (TSHR) hypermethylation in North Indian patients and investigate their association with clinicopathological characteristics.
Part of the book: Thyroid Cancer
Genetic Alterations of RET: Possible Implications and Clinical Correlations in Thyroid Carcinogenesis
Thyroid cancers are malignant tumors in the thyroid gland. DNA polymorphisms are playing a decisive role in unscrambling the genomic basis of tumor formation and development in cancer. Thyroid cancer is influenced in a polygenic and low-penetrance manner by RET gene polymorphisms and this part of the world (North India) has not recorded any study regarding RET alterations in this very cancer. We assessed RET G691S (rs1799939), L769L (rs1800861) and S904S (rs1800863) polymorphisms by restriction fragment length polymorphism (RFLP) in order to explain their potential role in the diagnosis and prognosis of Papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). In RET G691S polymorphism, the total dissemination of variant alleles (GA + AA) was 62.9% in cases as related to 44.5% in controls (P < 0.05). RET L769L variant alleles (TG + GG) was 70% in cases versus 88% in controls (P < 0.05). In RET S904S, occurrence of variant alleles (CG + GG) was 56% in cases versus 44% in controls (P < 0.05). G691S and L769L polymorphism advocate a “Dominant mode of inheritance”. The S904S polymorphism approves an “Additive mode of inheritance”. In conclusion, there was an over-representation of RET G691S/S904S polymorphisms and under-representation of L769L polymorphism in PTC and FTC patients. Additionally, our data suggest that some haplotypes (A T G, G T G and A T C) of RET may act as low penetrance alleles for predisposition of thyroid cancer.
Part of the book: Knowledges on Thyroid Cancer