Genetic Aberration Analysis in Thai Colorectal Adenoma and Early-Stage Adenocarcinoma Patients by Whole-Exome Sequencing
AbstractColorectal adenomas are precursor lesions of colorectal adenocarcinoma. The transition from adenoma to carcinoma in patients with colorectal cancer (CRC) has been associated with an accumulation of genetic aberrations. However, criteria that can screen adenoma progression to adenocarcinoma are still lacking. This present study is the first attempt to identify genetic aberrations, such as the somatic mutations, copy number variations (CNVs), and high-frequency mutated genes, found in Thai patients. In this study, we identified the genomic abnormality of two sample groups. In the first group, five cases matched normal-colorectal adenoma-colorectal adenocarcinoma. In the second group, six cases matched normal-colorectal adenomas. For both groups, whole-exome sequencing was performed. We compared the genetic aberration of the two sample groups. In both normal tissues compared with colorectal adenoma and colorectal adenocarcinoma analyses, somatic mutations were observed in the tumor suppressor gene APC (Adenomatous polyposis coli) in eight out of ten patients. In the group of normal tissue comparison with colorectal adenoma tissue, somatic mutations were also detected in Catenin Beta 1 (CTNNB1), Family With Sequence Similarity 123B (FAM123B), F-Box And WD Repeat Domain Containing 7 (FBXW7), Sex-Determining Region Y-Box 9 (SOX9), Low-Density Lipoprotein Receptor-Related Protein 5 (LRP5), Frizzled Class Receptor 10 (FZD10), and AT-Rich Interaction Domain 1A (ARID1A) genes, which are involved in the Wingless-related integration site (Wnt) signaling pathway. In the normal tissue comparison with colorectal adenocarcinoma tissue, Kirsten retrovirus-associated DNA sequences (KRAS), Tumor Protein 53 (TP53), and Ataxia-Telangiectasia Mutated (ATM) genes are found in the receptor tyrosine kinase-RAS (RTK–RAS) signaling pathway and p53 signaling pathway, respectively. These results suggest that APC and TP53 may act as a potential screening marker for colorectal adenoma and early-stage CRC. This preliminary study may help identify patients with adenoma and early-stage CRC and may aid in establishing prevention and surveillance strategies to reduce the incidence of CRC. View Full-Text
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Description: Table S1: Cancer related genes in chromosome 20
Externally hosted supplementary file 2
Description: Table S2: Somatic mutation master table
Externally hosted supplementary file 3
Description: Table S3: Predicted candidate genes with driver mutation
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Description: Figure S1: Data flow of the project
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Intarajak, T.; Udomchaiprasertkul, W.; Bunyoo, C.; Yimnoon, J.; Soonklang, K.; Wiriyaukaradecha, K.; Lamlertthon, W.; Sricharunrat, T.; Chaiwiriyawong, W.; Siriphongpreeda, B.; Sutheeworapong, S.; Kusonmano, K.; Kittichotirat, W.; Thammarongtham, C.; Jenjaroenpun, P.; Wongsurawat, T.; Nookaew, I.; Auewarakul, C.; Cheevadhanarak, S. Genetic Aberration Analysis in Thai Colorectal Adenoma and Early-Stage Adenocarcinoma Patients by Whole-Exome Sequencing. Cancers 2019, 11, 977.
Intarajak T, Udomchaiprasertkul W, Bunyoo C, Yimnoon J, Soonklang K, Wiriyaukaradecha K, Lamlertthon W, Sricharunrat T, Chaiwiriyawong W, Siriphongpreeda B, Sutheeworapong S, Kusonmano K, Kittichotirat W, Thammarongtham C, Jenjaroenpun P, Wongsurawat T, Nookaew I, Auewarakul C, Cheevadhanarak S. Genetic Aberration Analysis in Thai Colorectal Adenoma and Early-Stage Adenocarcinoma Patients by Whole-Exome Sequencing. Cancers. 2019; 11(7):977.Chicago/Turabian Style
Intarajak, Thoranin; Udomchaiprasertkul, Wandee; Bunyoo, Chakrit; Yimnoon, Jutamas; Soonklang, Kamonwan; Wiriyaukaradecha, Kriangpol; Lamlertthon, Wisut; Sricharunrat, Thaniya; Chaiwiriyawong, Worawit; Siriphongpreeda, Bunchorn; Sutheeworapong, Sawannee; Kusonmano, Kanthida; Kittichotirat, Weerayuth; Thammarongtham, Chinae; Jenjaroenpun, Piroon; Wongsurawat, Thidathip; Nookaew, Intawat; Auewarakul, Chirayu; Cheevadhanarak, Supapon. 2019. "Genetic Aberration Analysis in Thai Colorectal Adenoma and Early-Stage Adenocarcinoma Patients by Whole-Exome Sequencing." Cancers 11, no. 7: 977.
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