Abstract 4395: Somatic genomic alteration of 412 cancer-targeted genes of periampullary and pancreatic ductal adenocarcinoma in Indian patient population
Authors: Sikdar Nilabja , Saha Gourab , Singh Richa , Anchlia Dhiraj , Roy Paromita , Ghatak Supriyo , Banerjee Sudeep , Gulati Sumit , Ghosh Shibajyoti 
Published: July 2017

Abstract
Introduction: Pancreatic Ductal Adenocarcinoma (PDAC), the most common primary malignant disease of the pancreas and the periampullary region, accounts for about 75% of all nonendocrine tumors arising in this region. It is 4th most lethal malignancies. The 5 year survivability rate is below 5%. At the beginning of the 21st century, the estimated number of PC worldwide was 110,000, with an estimated global mortality rate of 98%. Incidence of periampullary adenocarinoma (PACs) is low, approximately 0.5-2% of all gastrointestinal malignancies and 20% of all tumors of the extrahepatic biliary tree.
Aims & Objectives: To identify the somatic single nucleotide variants (SNV’s) in 412 cancer related genes in PDAC & PAC’s. To identify possible altered biological pathways enriched in these cancers.
Methodology: DNA samples from Tissue and blood were sequenced for exon sequencing of 412 cancer related genes (NIMBLGNE panel, Custom). Raw fastq files processed using GATK tools and variants identified by Varscan2, & MuTect. Altered pathways identified by KEEG.
Result: A total 105 Somatic exonic Single Nucleotide Variants (SNV’s), 9 somatic exonic Indels, 22 LOH mutations (both Indel and SNV’s) were identified in our sample set. Among the candidate genes of PDAC somatic SNV’s were found in TP53, SMAD4 in some patient whereas frequency of KRAS mutation was less frequent. Fourteen SNV’s were reported in cosmic database which includes 5 pathogenic variants, whereas 91 SNV’s were novel. A total 75 non-synonymous, 6 stopgain, and 24 synonymous SNV’s were observed among 105 SNV’s. Fifty eight percent of transversion and 52% of transition observed from all SNVs. Among all transversion fifty five percent SNV’s were C&gt;T, G&gt;T. PI3-Akt, Proteoglycans in cancer, Transcription misregulation, Rap1, ErbB, Neurotrophin pathways were found to be most commonly enriched in our patient population. Our data strongly suggest PI3-Akt, Proteoglycans in cancer pathways play a critical role in the disease.
Conclusion: This study implicates a landscape of somatic SNV’s in PDAC’s and PAC’s and alteration of biological pathways in our patient population. We also observeed ERBB2 and KMT2C genes are predominantly alerted in PDAC’s and PAC’s. P53, KRAS and SMAD4 are the known mutated genes contributes very similar mutational pattern.
Citation Format: Nilabja Sikdar, Gourab Saha, Richa Singh, Dhiraj Anchlia, Paromita Roy, Supriyo Ghatak, Sudeep Banerjee, Sumit Gulati, Shibajyoti Ghosh. Somatic genomic alteration of 412 cancer-targeted genes of periampullary and pancreatic ductal adenocarcinoma in Indian patient population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4395. doi:10.1158/1538-7445.AM2017-4395