Abstract 612: Interrogating the molecular profile of colorectal cancer tumors in Puerto Rican Hispanics
Authors: Montes-Rodriguez Ingrid M. , Centeno-Girona Hilmaris , Rivera-Lynch Camila , Soto-Salgado Marievelisse , Rivera Noridza , Cruz-Correa Marcia 
Published: July 2021

Abstract
Background: Colorectal cancer (CRC) is the second and third most common diagnosed cancer in males and females, respectively, and is the second leading cause of cancer-related deaths in Puerto Rico (PR). This differs from USA, were CRC is the third most commonly diagnosed cancer and the third leading cause of cancer-related deaths for men and woman, respectively. CRC is a heterogeneous disease and the genetic characteristics of the tumors are considered to evaluate prognostic outcome and selection of targeted therapies. Currently, techniques such as next-generation sequencing (NGS) are being used for tumor profiling, in order to classify and identify driver genetic mutations in CRC patients. Even though there have been numerous studies that have use genetic profiling to classify and to identify driver genetic mutations for CRC, comprehensive genetic profiling of cancer patients in the Hispanic population of PR has not been performed.
Methods: We retrospectively evaluated the mutational profile of CRC tumors from 218 Puerto Rican Hispanics (PRH) that underwent NGS testing from 2015 to 2020. The data was provided by CARIS Life Sciences that uses a 592 gene panel in order to detect mutations, indels and copy number variants (CNV). We estimated the prevalence of somatic mutations of PRH CRC tumors and compared them with the mutational profiles reported for Colorectal Adenocarcinoma from the TCGA Pan-Cancer Clinical Data available in the cBioPortal for Cancer Genomics. Descriptive statistics were performed to characterize the database.
Results: For our population, 7.8% were diagnosed with CRC before 50 years of age (early-onset CRC) and 92.2% were diagnosed after 50 years of age. These analyses showed that the most commonly mutated genes for CRC tumors in PRH are APC (82%), TP53 (76%), KRAS (56%), PIK3CA (18%), SMAD4 (13%), AMER1 (10%), FBXW7 (9%), BRAF (5%), RNF43 (4%), and MUTYH (4%). Several genes are shared among the top ten most mutated genes when comparing the CRC tumor mutational profiles from PRH with that reported in the CRC tumors from TCGA study, including APC, TP53, KRAS, and PIK3CA, having mutational frequencies of 73%, 59%, 41%, and 28%, respectively. The most common CNVs for PRH CRC tumors were CDX2 (20%), CDKN1B (7%), and HNRNPA2B1 (5%) genes. These CNVs have also been reported in the CRC TCGA Pan-Cancer study with frequencies of 6.4%, 0.3% and 0.3 % for CDX2, CDKN1B, and HNRNPA2B1 genes, respectively.
Conclusion: This study is the first to reports the mutational profile of CRC tumors from Puerto Rican Hispanics. CRC tumors from PRH and the TCGA study, which has only 0.8% of Hispanic/Latino patients, share mutated genes and CNV, although with different mutational frequencies. Understanding the most common carcinogenic molecular pathways that affect PRH with CRC is crucial to guide research efforts in the discovery of new therapeutic modalities.
Citation Format: Ingrid M. Montes-Rodriguez, Hilmaris Centeno-Girona, Camila Rivera-Lynch, Marievelisse Soto-Salgado, Noridza Rivera, Marcia Cruz-Correa. Interrogating the molecular profile of colorectal cancer tumors in Puerto Rican Hispanics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 612.