Abstract 740: Mutational landscape of early-onset colorectal cancer tumors in Hispanics
Authors: Gonzalez-Pons Maria , Rovira Lenis , Carrasquillo Kelvin , Montes Ingrid , Perez-Mayoral Julyann , Roche Abiel , Napoles Anna M. , Byun Jung S. , Pérez-Stable Eliseo , Gardner Kevin L. , Cruz-Correa Marcia 
Published: August 2019

Background: Colorectal cancer (CRC) is the 3rd and 1st leading cause of cancer-related deaths in men and women in the US and Puerto Rico, respectively. Although the incidence of CRC has been decreasing, annual CRC incidence rates have increased by more than 1.5% per year for more than a decade among patients 20 to 49 years old. Early-onset CRC represents a clinically distinct form of CRC often associated with a poor prognosis, which currently comprises 10% to 18% of newly diagnosed cases. Moreover, a marked increase in early-onset CRC incidence has been reported among Hispanics, compared to other racial/ethnic groups. The aim of this study was to perform whole exome sequencing analysis on sporadic, early-onset colorectal tumors and concordant healthy colonic mucosa in order to identify genetic variations that could contribute to the development of colorectal tumors at a younger age among Hispanics.

Methods: Whole exome sequencing analyses were performed on 42 concordant colorectal adenocarcinoma and colonic mucosa tissue samples from individuals diagnosed with colorectal cancer at &lt;50 years old to identify somatic and germinal mutations associated with early-onset colorectal cancer. All participants were recruited by PuertoRico Familial Colorectal Cancer Registry (PURIFICAR); only participants without known mutations in genes associated with hereditary cancer syndromes were included.

Results: A total of 14 shared somatic tumor-specific point mutations were detected in 16 of the 42 early-onset colorectal tumors analyzed. Six of these variants were located in introns and one was located in an intergenic region. When analyzing normal colonic mucosa, 26,716 shared point mutations were detected in all of the participants in our study. Of these, genetic variations were located in introns (16,443), exons (4,008), non-coding RNAs (3,516), promoters (3,467), intergenic regions (2,774), 3’ UTR (1,741), 5’ UTR (717), and splice sites (79).

Conclusion: This is the first description of the mutational landscape of early-onset colorectal tumors among Puerto Rican Hispanics, a Hispanic subgroup with a high burden of early-onset CRC. The majority of the mutations detected were not located in exons, suggesting that variations in genomic regions that regulate gene expression may contribute to early-onset carcinogenesis. Additional research is warranted to gain a more comprehensive understanding of the biology of sporadic, early-onset CRC in order to directly address this emerging public health problem and to subsequently shift current clinical practices for young patients across the cancer continuum, from prevention strategies to screening and/or treatment.

Citation Format: Maria Gonzalez-Pons, Lenis Rovira, Kelvin Carrasquillo, Ingrid Montes, Julyann Perez-Mayoral, Abiel Roche, Anna M. Napoles, Jung S. Byun, Eliseo Pérez-Stable, Kevin L. Gardner, Marcia Cruz-Correa. Mutational landscape of early-onset colorectal cancer tumors in Hispanics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 740.