Abstract 2183: Interrogating the molecular profile of colorectal cancer: detection of clinically actionable alterations in Hispanics
Authors: Montes-Rodriguez Ingrid M. , Centeno-Girona Hilmaris , Rivera-Lynch Camila , Rivera Noridza , Cruz-Correa Marcia 
Published: June 2022

Abstract
Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths among men and women and the third cause of cancer deaths in the US. Tumor profiling techniques have led to the identification of actionable alterations to guide treatment and improve survival in cancer patients. However, comprehensive genetic profiling of colorectal cancer tumors from Hispanics living in Puerto Rico (PRH) has not been performed. Our study aimed at understanding the common CRC carcinogenic molecular pathways that affect our Hispanic population by evaluating colorectal tumors from molecularly characterized ethnically diverse cohorts.
Methods: We retrospectively evaluated the mutational profile of CRC tumors from 218 PRH that underwent NGS testing from 2015 to 2020 (provided by CARIS Life Sciences and the Precision Oncology Alliance). We estimated the prevalence of somatic mutations of PRH CRC tumors and compared them with those reported in The Cancer Genome Atlas (TCGA) Pan-Cancer Atlas Clinical Data and the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE), both available through the cBioPortal for Cancer Genomics. Descriptive statistics were performed to characterize the database.
Results: Among the top mutated genes for CRC tumors in PRH were APC (81.9%, n=182), TP53 (75.3%, n=178), KRAS (56.2%, n=185), PIK3CA (18.0%, n=178) and SAMD4 (12.6%, n=175). For PRH, the most frequent gene amplifications were: CDX2 (20.1%, n=184), CDKN1B (6.6%, n=183), and HNRNPA2B1 (5.4%, n=184). Significant differences in the mutational frequencies of CRC driver genes, such as APC, TP53, PIK3CA, FBXW7, CDX2, CDKN1B, and HNRNPA2B1, and actionable genes, such as KRAS/NRAS, BRAF and for ERBB2 amplifications, among PRH were observed when compared to the TCGA and GENIE datasets. The prevalence of MSI tumors for PRH was 2.0%.
Conclusion: This is the first study to report the mutational profile of CRC tumors from PRH and to describe differences in mutational frequencies when compared other non-Hispanic and U.S. mainland Hispanic populations using data from TCGA and GENIE. Differences in prevalence of immunotherapy and targeted associated biomarkers may contribute to the observed disparities in survival and response to therapies. Understanding the most common carcinogenic molecular pathways that affect Hispanics with CRC is crucial to guide research efforts in the development of new therapeutic modalities incorporating genomically diverse populations.
Citation Format: Ingrid M. Montes-Rodriguez, Hilmaris Centeno-Girona, Camila Rivera-Lynch, Noridza Rivera, Marcia Cruz-Correa. Interrogating the molecular profile of colorectal cancer: detection of clinically actionable alterations in Hispanics [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 2183.