Abstract 2277: Evaluation of mutation profile of oncogenic signalling pathway in breast cancer among Indian population
Authors: Kumar Rahul , Srivastava Anurag , Agrawal Usha , Deo S.V.S. , Mathur Sandeep R. , Gogia Ajay , Tanwar Pranay 
Published: June 2022

Abstract
Introduction: Genomic profile of breast cancer is diverse in nature and complex due to heterogeneity among racial groups. In India, it is the leading cause of cancer death and accounts for 13.5% of the total incidence of new cancer cases with a mortality rate of 10.6% irrespective of age and sex in 2020. The growing incidence marks the importance of profiling driver genes that are usually involved in proliferation, cell survival, oxidative stress response, progenitor phenotype, cell growth, apoptosis, and cell cycle regulation. In order to evaluate the mutation profile within breast tumor, we carried out Whole Exome Sequencing (WES) followed by gene analysis which is implicated in oncogenic pathways.
Experimental procedures: 40 primary breast cancer patients were recruited from the clinical follow-up at AIIMS, New Delhi, India. With informed consent, tumor and blood were collected after surgery followed by genomic DNA extraction. Library preparation was done by adopting a protocol developed by Illumina. Exonic regions were captured by using Trueseq Exome kit which covers ≥ 80% of whole-exome and sequencing was performed by utilizing Illumina platform as per the manufacturer’s instruction. Bioinformatics analyses were carried out through an in-house developed pipeline. We identified altered genes by comparing them with the matched control and further filtered them on the basis of their functional impact.
Results: In our study, a recurrent mutation in RTK-RAS, Notch, PI3K, WNT, Hippo, Myc, cell cycle, p53, TGF-β, NRF2 pathways were reported among 40 individuals. We found a total of 263 altered genes, out of these 186 genes were driver genes comprise 88 tumor suppressor genes and 98 oncogenes while the rest are passenger genes. In terms of SNP Class- &gt;58%- missense, &lt;4%-silent, &lt;38%-nonsense mutations. These SNPs have their phenotypic impact such as high, moderate, modifier, and low which accounts &lt;2.4%, 8-12%, &gt;75%, and &lt;10% respectively. Missense mutation has a greater fraction of C&gt;T transitions followed by C&gt;A transversion. Moreover, we also identified p53, PIK3CA, EIF4EBP1 and ALK as a top mutated genes. A hotspot mutation H1047R in PIK3CA and R56W, as well as R99S in EIF4EBP1, were account for subsequently 20%, 25%, and 15% samples along with hotspot region in MAML3.
Conclusions: Here we demonstrate exclusive molecular profiling of the oncogenic pathways of breast cancer in the Indian population. Apart from nonsynonymous substitution, we also revealed recurrent mutation within a specific position or region of gene involved in the RTK-RAS, Notch, and PIK3CA network. Overall this study will improve insight for commonly mutated genes with a primary objective of screening, diagnosis, prognosis along risk stratification. In addition, this could be used to identify specific targetable candidate mutation gene panels with an overall objective of personalized drug therapy.
Citation Format: Rahul Kumar, Anurag Srivastava, Usha Agrawal, S.V.S. Deo, Sandeep R. Mathur, Ajay Gogia, Pranay Tanwar. Evaluation of mutation profile of oncogenic signalling pathway in breast cancer among Indian population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2277.