Whole-Exome Sequencing Characterized the Landscape of Somatic Mutations and Pathways in Colorectal Cancer Liver Metastasis

الملخص EN

Purpose.

Liver metastasis remains the leading cause of cancer-related mortality in colorectal cancer.

The mechanism of occurrence and development of liver metastasis from colorectal cancer is unclear.

Methods.

The primary tumor tissues and blood samples of 8 patients with liver metastasis of colorectal cancer were collected, followed by nucleic acid extraction and library construction.

Whole-exome sequencing was performed to detect the genomic variations.

Bioinformatics was used to comprehensively analyze the sequencing data of these samples, including the differences of tumor mutation burden, the characteristics of gene mutations, and signaling pathways.

Results.

The results showed that the top three genes with the highest mutation frequency were TP53, APC, and KRAS.

Tumor mutation burden of this study, with a median of 8.34 mutations per MB, was significantly different with The Cancer Genome Atlas databases.

Analysis of molecular function and signaling pathways showed that the mutated genes could be classified into five major categories and 39 signaling pathways, involving in Wnt, angiogenesis, P53, Alzheimer disease-presenilin pathway, notch, and cadherin signaling pathway.

Conclusions.

In conclusion, we identified the extensive landscape of altered genes and pathways in colorectal cancer liver metastasis, which will be useful to design clinical therapy for personalized medicine.