Genetic aberration analysis in thai colorectal adenoma and early-stage adenocarcinoma patients by whole-exome sequencing
Journal article, 2019
Colorectal 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.
Screen marker
Early-stage colorectal adenocarcinoma
Colorectal adenoma
Somatic mutation
Author
Thoranin Intarajak
Chulabhorn Royal Academy
King Mongkut's University of Technology Thonburi
Wandee Udomchaiprasertkul
Chulabhorn Royal Academy
Chakrit Bunyoo
Chulabhorn Royal Academy
Jutamas Yimnoon
Chulabhorn Royal Academy
Kamonwan Soonklang
Chulabhorn Royal Academy
Kriangpol Wiriyaukaradecha
Chulabhorn Royal Academy
Wisut Lamlertthon
Chulabhorn Royal Academy
Thaniya Sricharunrat
Chulabhorn Hospital
Worawit Chaiwiriyawong
Chulabhorn Hospital
Bunchorn Siriphongpreeda
Chulabhorn Royal Academy
Sawannee Sutheeworapong
King Mongkut's University of Technology Thonburi
Kanthida Kusonmano
King Mongkut's University of Technology Thonburi
Weerayuth Kittichotirat
King Mongkut's University of Technology Thonburi
Chinae Thammarongtham
Thailand National Center for Genetic Engineering and Biotechnology (BIOTEC)
Piroon Jenjaroenpun
University of Arkansas for Medical Sciences
Thidathip Wongsurawat
University of Arkansas for Medical Sciences
Intawat Nookaew
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
University of Arkansas for Medical Sciences
Chirayu Auewarakul
Chulabhorn Royal Academy
S. Cheevadhanarak
King Mongkut's University of Technology Thonburi
Cancers
20726694 (eISSN)
Vol. 11 7 977Subject Categories
Medical Genetics
Cancer and Oncology
Genetics
DOI
10.3390/cancers11070977