Abstract PR15: Intratumoral heterogeneity in Latino gastric adenocarcinomas

Abstract

Abstract The goal of this study was to examine gastric (stomach) cancer mutational intratumoral heterogeneity (ITH) in Latinos using multiregion sequencing (MSEQ). Gastric cancer is the 2nd leading cause of cancer-related death worldwide. It is diagnosed in 25,000 Americans each year, with Latinos twice as likely to succumb as Whites. Treatment is currently limited to a few molecularly guided therapies, but TCGA data show that 70% of GC patients have a mutation in a gene targetable with existing drugs. Significant ITH has been identified in a variety of tumor types to date, although a GC study has yet to be published. ITH is an important consideration for personalized therapy. Driver gene mutations are frequently found to be nonclonal, a crucial factor when assessing effective druggability. In this study, two to five tumor biopsies and adjacent normal tissue were obtained from 33 Latino patients, totaling 120 tumor (T) biopsies and 33 normal (N) samples. DNA was extracted from the tissues and the coding regions of 762 cancer-related genes were sequenced using Agilent target enrichment and Illumina sequencing. For each biopsy, estimates were made of sample purity and ploidy, somatic mutations were called using joint analysis of all T and N sequence data for each patient, cancer cell fraction (CCF) was estimated for each mutation, and copy number variation (CNV) was called across the genome. Somatic mutations and copy number changes were analyzed for clonality in each patient. We found a high degree of heterogeneity, both intratumoral and interpatient, with the fraction of functional somatic mutations that are clonal ranging from 0 to 68%, the fraction private to one biopsy ranging from 32% to 100%, and the fraction shared between multiple but not all biopsies ranging from 0 to 42%. For 10 of the 33 samples there was at least one gene, containing a clonal functional mutation, for which there is an FDA-approved targeted therapy. In summary, our study is the first to assess ITH in GC. Our results are important to understand the genetic diversity and clonal architecture of these tumors and to improve molecular diagnostics. This abstract is also being presented as Poster D107. Citation Format: Ted Toal, Guadalupe P. Echeverry, Ruta Sahasrabudhe, Mabel Bohorquez, Javier Torres, Shiro Urayama, Amanda Kirane, Magdalena Echeverry, Luis G. Carvajal Carmona. Intratumoral heterogeneity in Latino gastric adenocarcinomas [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr PR15.