Comprehensive genomic profiling reveals prognostic signatures and insights into the molecular landscape of colorectal cancer

• DOI: 10.3389/fonc.2023.1285508
• Publication Date: 2023-11-14T03:27:06Z
• Authors: Jinwei Yang; Sihui Zhao; Junyan Su; Siyao Liu; Zaozao Wu; Wei Ma; Ming Tang; Jingcui Wu; Erdong Mao; Li Han; Mengyuan Liu; Jiali Zhang; Lei Cao; Jingyi Shao; Yun Shang
• Keywords: GNAQ

Colorectal cancer (CRC) is a prevalent malignancy with diverse molecular characteristics. The NGS-based approach enhances our comprehension of genomic landscape CRC and may guide future advancements in precision oncology for patients.In this research, we conducted an analysis using Next-Generation Sequencing (NGS) on samples collected from 111 individuals who had been diagnosed CRC. We identified somatic germline mutations structural variants across the tumor genomes through comprehensive profiling. Furthermore, investigated driver their potential clinical implications.Our findings underscore intricate heterogeneity genetic alterations within Notably, BRAF, ARID2, KMT2C, GNAQ were associated prognosis. Patients harboring or KMT2C exhibited shorter progression-free survival (PFS), whereas those experienced worse overall (OS). unveiled 80 co-occurring three mutually exclusive significant gene pairs, enriched primarily pathways such as TP53, HIPPO, RTK/RAS, NOTCH, WNT, TGF-Beta, MYC, PI3K. co-mutations BRAF/ALK, BRAF/NOTCH2, BRAF/CREBBP, BRAF/FAT1 correlated PFS. AR 37 (33.33%) patients, carriers these displayed diminished PFS OS. Decreased protein expression was observed cases mutations. A four-gene mutation signature established, incorporating aforementioned prognostic genes, which emerged independent determinant via univariate multivariate Cox regression analyses. Noteworthy BRAF ARID2 decreases detected patients respective mutations.The integration analyses furnishes crucial insights into CRC's characteristics, drug responsiveness, construction predicting