1. Gachon Institute of Genome Medicine and Science, Gachon University Gil Medical Center, Incheon, Republic of Korea
2. Gachon Advanced Institute for Health Science and Technology, Gachon University, Incheon, Republic of Korea
3. Department of Surgery, Gachon University College of Medicine Gil Medical Center, Incheon, Republic of Korea
4. Department of Pathology, Gachon University College of Medicine Gil Medical Center, Incheon, Republic of Korea
5. Department of Microbiology, Gachon University College of Medicine, Incheon, Republic of Korea
6. Department of Internal Medicine, Gachon University College of Medicine Gil Medical Center, Incheon, Republic of Korea
7. Department of Genome Medicine and Science, Gachon University College of Medicine, Incheon, Republic of Korea
* These authors equally contributed as first authors.
Purpose: Effective treatment of colorectal cancer could benefit from understanding molecular characteristics including mutation profiles of important genes. This study aimed to explore the molecular characteristics of colorectal cancer based on next generation sequencing.
Methods: The mutational characteristics by targeted next generation sequencing in 172 colorectal tumor samples from Korean patients were evaluated to explore their associations with clinical features. Targeted sequencing of 375 genes was performed with an average target-depth of 800X.
Results: TP53 and APC showed higher mutation frequencies from the left-sided tumors, while CTNNB1 were more frequent from the right-sided tumors. The tumor suppressor NOTCH1 and the DNA strand break repair gene PALB2 were more frequently mutated in early onset tumors. KRAS and PTEN mutations were more frequent from patients with advanced cancers by cancer antigen markers. TP53 and BRAF mutations were more frequent from patients of T3 and T4 stages, where their variant allele fractions were generally higher in T4 tumors, implying that advanced tumors have higher fraction of cancer cells with TP53 and BRAF mutations. Mutational profiles of these patients were also assessed with other clinical features. Comparison of mutational characteristics with the Caucasian subjects from independent data showed that the identified mutational characteristics are largely Korean-specific except for a few key colorectal cancer genes.
Conclusion: Next generation sequencing-based targeted sequencing can provide valuable information on molecular characterization of colorectal cancer patients, and its clinically relevant information can provide benefits to better understand colorectal cancer.
Keywords: Colorectal cancer, targeted sequencing, mutation, Korean population