AI Summary
The article discusses the largest multi-omics study on colorectal cancer to date, conducted by the Institute of Intelligent Medical Research in collaboration with Uppsala University. The research identified new genetic landscapes, including 96 mutated driver genes, 9 previously unknown in CRC, and 24 new to any form of cancer. Specific mutation patterns unique to CRC were also discovered, along with pathways linked to patient survival rates. The researchers developed a new molecular classifier system based on these findings, leading to the identification of five distinct CRC prognostic subtypes. This classification system is expected to improve the diagnosis and treatment of colorectal cancer.
The Institute of Intelligent Medical Research (IIMR) of BGI Genomics, in collaboration with Sweden’s Uppsala University, has published the largest multi-omics study of colorectal cancer (CRC) to date. The study aimed to understand the functional and prognostic impact of cancer-causing somatic mutations, revealing new genetic alterations and developing a new molecular classifier of tumor variants. This research was published in the journal Nature on August 7th, 2024.
Unveiling new genetic landscapes
The researchers analyzed the whole genomes and transcriptomes of 1,063 primary colorectal cancers within a population-based cohort, with 94% of the patients completing a 5-year clinical follow-up. This extensive analysis identified 96 mutated driver genes, 9 of which were previously unknown in CRC, and 24 that were new to any form of cancer.
Several specific mutation patterns that are unique to CRC were identified. Mutations in specific pathways (WNT, EGFR, TGFβ), a mitochondrial gene (CYB), three regulatory elements, 21 copy-number variations (alterations in the number of copies of a particular gene), and a specific mutation signature (COSMIC SBS44) were linked to patient survival rates.
New molecular classifier system
Building on these findings, the researchers developed a new strategy to molecularly classify colorectal cancer. Through an integrated analysis that combined mutated genes with gene expression levels, they identified five distinct CRC prognostic subtypes (CRPSs), each with unique molecular characteristics. This new classification system is poised to revolutionize the way CRC is diagnosed and treated.
A comprehensive understanding of disease progression
Through timing analysis, the study uncovered that specific genetic alterations, such