Molecular characterization of colorectal cancer using whole‐exome sequencing in a Taiwanese population

Abstract

Next‐generation sequencing (NGS) technology is currently used to establish mutational profiles in many heterogeneous diseases. The aim of this study was to evaluate the mutational spectrum in Taiwanese patients with colorectal cancer (CRC) to help clinicians identify the best treatment method. Whole‐exome sequencing was conducted in 32 surgical tumor tissues from patients with CRC. DNA libraries were generated using the Illumina TruSeq DNA Exome, and sequencing was performed on the Illumina NextSeq 500 system. Variants were annotated and compared to those obtained from publicly available databases. The analysis revealed frequent mutations in APC (59.38%), TP53 (50%), RAS (28.13%), FBXW7 (18.75%), RAF (9.38%), PIK3CA (9.38%), SMAD4 (9.38%), and SOX9 (9.38%). A mutation in TCF7L2 was also detected, but at lower frequencies. Two or more mutations were found in 22 (68.75%) samples. The mutation rates for the WNT, P53, RTK‐RAS, TGF‐β, and PI3K pathways were 78.13%, 56.25%, 40.63%, 18.75%, and 15.63%, respectively. RTK‐RAS pathway mutations were correlated with tumor size ( P = 0.028). We also discovered 23 novel mutations in NRAS , PIK3CA , SOX9 , APC , SMAD4 , MSH3 , MSH4 , PMS1 PMS2 , AXIN2 , ERBB2 , PIK3R1 , TGFBR2 , and ATM that were not reported in the COSMIC, The Cancer Genome Atlas, and dbSNP databases. In summary, we report the mutational landscape of CRC in a Taiwanese population. NGS is a cost‐effective and time‐saving method, and we believe that NGS will help clinicians to treat CRC patients in the near future.

Enhancing the landscape of colorectal cancer using targeted deep sequencing

“…A recent Chinese study on CRC using whole exome sequencing (WES) revealed mutation rate of 59.38% in APC, which is similar to our study result 20 . In addition, the mutation rate TP53 is 50%, which is lower than that of our cohort.…”

Discovery of core gene families associated with liver metastasis in colorectal cancer and regulatory roles in tumor cell immune infiltration

“…In a study of serum samples, the expression of MMP12 was proportional to the progression of colon cancer, which was higher in patients suffering from vascular invasion than their V0-stages counterparts [67] . Mutated MSH4 was detected in CRC patients [68] , another case report described a metastatic bladder cancer patient with MSH4 mutation who demonstrated complete response to PD-L1 blockade [69] . TERM-1 could boost immune responses during pro-inflammatory processes, neutrophils who expressed high level of TREM-1 was proposed as a promoting factor in CRC development [70] .…”

Genomic Alteration Characterization in Colorectal Cancer Identifies a Prognostic and Metastasis Biomarker: FAM83A|IDO1

“…Out of these 28 genes, 18 genes have been reported in at least one CRC-associated study, such as APC, TP53, KRAS, SYNE1, PIKSCA, FBXW7, etc. (33)(34)(35)(36)(37)(38)(39). In addition, 10 novel drivers were identified: DNAH11, USHA2, HMCN1, HYDIN, MDN1, DST, VPS13B, DNAH8, EYS, and NBEA.…”