Unveiling the role of in Chinese colorectal cancer patients: a positive influence on tumor mutational burden.

Transl Cancer Res

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

Published: September 2024

AI Article Synopsis

  • * Researchers sequenced data from 94 CRC patients and found high mutation rates in several key oncogenes, specifically noting the G12D subtype had a higher mutation rate than others.
  • * The findings suggest that TMB influenced by co-mutations may serve as a valuable biomarker for predicting the effectiveness of immunotherapy treatments in CRC patients, particularly with the presence of specific co-mutations.

Article Abstract

Background: One of the main challenges associated with the development of therapeutic and diagnostic strategies for patients with colorectal cancer (CRC) is the establishment of minimally invasive and efficient biomarkers. Pertinent genes in CRC have been identified through their functions in systematic mutagenesis screens. is considered a dominant mutated oncogene that contributes to pathogenesis of CRC. This study aimed to explore the genomic alternations of in a CRC population.

Methods: Sequencing data of 94 Chinese patients with CRC were prospectively collected and analyzed using next-generation sequencing (NGS). The influence of and its associated subtype co-mutations on the expression level of the tumor mutational burden (TMB) was investigated. The objective of our study was to assess the potential prognostic significance of and other driving oncogenes in determining the clinical efficacy of immunotherapy.

Results: The gene mutation rates of , , and were 81.91%, 71.28%, and 43.62%, respectively. Additionally, G12D displayed a relatively higher mutation rate than other -mutant subtypes. Increased TMB was observed in cases of and mutation combined with single mutation; furthermore, the expression of TMB in G12V was the highest, and G12D presented the lowest TMB in single -mutant subtypes or the combination with mutations.

Conclusions: The TMB driven by co-mutations may have the potential to be used as a key biomarker for prediction of treatment outcomes of immune checkpoint inhibitors (ICIs) in patients with CRC, especially with co-mutation.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483435PMC
http://dx.doi.org/10.21037/tcr-24-600DOI Listing

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