Abstract 6463: Highly frequent gene mutations and co-occurring genes analysis in colorectal cancer

Abstract Background: Colorectal cancer (CRC) is the second most leading cause of cancer-related deaths worldwide. Understanding the molecular alterations that drive CRC is critical for improving patient outcomes. Next-generation sequencing (NGS) has revolutionized CRC molecular profiling by simultaneous analysis of multiple genes with high accuracy and sensitivity. In this study, we analyzed a cohort of CRC formalin-fixed paraffin-embedded (FFPE) samples to identify highly frequent gene mutations and co-occurring genes in CRC. Methods: FFPE samples from CRC patients tested from January 2020 to May 2023 were analyzed using NeoTYPE® Colorectal Tumor Profile. This profile analyzes 44 biomarkers through a combination of NGS focusing on a panel of 36 genes known to be frequently mutated in CRC, as well as 3 FISH and 3 IHC biomarkers. Gene mutation frequency, co-occurring mutation genes and clinical significance were explored and analyzed. In addition, immunotherapy markers, Microsatellite Instability (MSI) and Tumor Mutation Burden (TMB) were assessed. Results: A total of 2, 920 patients (1, 577 men and 1, 343 women) with CRC were included in this study. Average sequence coverage was 2386X with mean minor allelic frequency of 30%. A higher average number of variant allele frequency were observed in metastatic versus primary colorectal cancer (P. 001). We found that APC, TP53, KRAS, PIK3CA and ARID1A were the most frequently mutated genes. APC truncated mutation p. R1450* were the most common mutations. KRAS, PIK3CA and TP53 missense mutations are the prevalent consequence. Notably, a subset of patients exhibited high microsatellite instability (MSI-H) or TMB high, indicating potential eligibility for immune checkpoint inhibitor therapy. In addition, we found APC mutations co-occurring with TP53 or KRAS mutations (p. 001) in our cohort. Conclusion: Our results provide insight into the genetic landscape of CRC and highlight the importance of understanding co-occurring mutations in this disease. Specifically, APC mutations frequently coincide with TP53 mutations, jointly contributing to the onset of CRC. TP53 often play a role in promoting genomic instability and evading mechanisms that regulate cell growth. The identification of highly frequent mutations and co-occurring genes may have important implications for the development of targeted therapies and personalized treatment approaches for CRC patients. Citation Format: Qinqin Zha, Frank Scarpa, Madhu Rengaraj, Anna Juncker-Jensen. Highly frequent gene mutations and co-occurring genes analysis in colorectal cancer 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 (6Suppl): Abstract nr 6463.