Abstract 3932: Multi-omics characterization of molecular features and global-local genomic ancestry analysis of colorectal cancer in Hispanic-Latinos
Authors: Villarreal Enrique I. Velazquez , Rajpara Seeta , Jin Yuxin , Postel Mackenzie , Waldrup Brigette , Wu Flemming , Loza Donna , Lenz Heinz-Josef , Craig David W. , Carpten John D. 
Published: March 2024

Abstract
Introduction: Clinical factors and molecular characteristics play pivotal roles in shaping therapeutic strategies and prognoses in colorectal cancer (CRC), the second leading cause of cancer-related mortality in the United States. Despite an overall decline in mortality, the Hispanic/Latino (H/L) population in the Los Angeles area exhibits mortality rates up to 20% higher than their Caucasian American counterparts, often with diagnoses at a younger age and advanced disease stages. Few studies have utilized substantial H/L sample sizes and integrated comprehensive clinical and multi-omics data to conduct integrative translational analysis of reported genomic alterations and their implications for colorectal tumorigenesis.
Methods: We collected clinical, DNA, and RNA sequencing data from 36 primary CRC Tumor/Normal (T/N) samples and 82 primary CRC T/N samples within the H/L population in the Los Angeles area through the Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network and the Oncology Research Information Exchange Network (ORIEN), respectively. Additionally, we retrieved two CRC samples with spatial transcriptomic (ST) data from the 10xGenomics database. This data underwent Whole Exome and RNA sequencing analysis. Furthermore, we conducted global and local genomic ancestry analyses to establish correlations between self-ancestral identification and the five main superpopulations. ST data was analyzed using recently released bioinformatics tools. Clinical and genomic data were integrated.
Results: In these studies, distinct age-of-onset, Amerindian (AMR), and survival patterns were observed, with significant mutations identified in key genes, including APC, TP53, KRAS, and PIK3CA. Cancer heterogeneity was evident, influenced by mutation type, microsatellite instability, subsite, and ethnicity. Ancestry analysis indicated genetic diversity, with a predominant AMR heritage and cases showcasing substantial European genetic proportions alongside AMR ancestry. Additionally, RNA sequencing has been conducted, with ongoing transcriptomic analysis in both studies, and the results are set for presentation at the annual meeting. The ST analysis generated initial maps, delineating diverse cellular populations and revealing the samples' distinct immunological and inflammatory signals.
Conclusion: Our study has delved into the molecular profiling of CRC tumors among H/L patients, contributing essential insights into the DNA and RNA level characterization of CRC tumors and the multifaceted clinical and genomic heterogeneity within our aimed population. It also provides crucial insights into CRC tumor heterogeneity and the tumor microenvironment. These findings serve as the cornerstone for forthcoming sample analyses within our PE-CGS project to potentially lead to the development of personalized treatments.
Citation Format: Enrique I. Velazquez Villarreal, Seeta Rajpara, Yuxin Jin, Mackenzie Postel, Brigette Waldrup, Flemming Wu, Donna Loza, Heinz-Josef Lenz, David W. Craig, John D. Carpten. Multi-omics characterization of molecular features and global-local genomic ancestry analysis of colorectal cancer in Hispanic-Latinos [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3932.