Abstract
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.
Highlights
Colorectal cancer (CRC) is the third most common cancer worldwide, with increasing numbers of estimated new cases in both males and females [1]
The intersection of a gene with somatic mutations between the matched normal-colorectal adenoma and matched normal-colorectal cancer (CRC) were enriched in the focal adhesion pathway, protein digestion and absorption pathway, and PI3K-Alt signaling pathway (Figure 1)
The intersection of a gene with somatic mutations between the matched normal4 of 17 colorectal adenoma and matched normal-CRC were enriched in the focal adhesion pathway, protein digestion and absorption pathway, and PI3K-Alt signaling pathway (Figure 1)
Summary
Colorectal cancer (CRC) is the third most common cancer worldwide, with increasing numbers of estimated new cases in both males and females [1]. The five-year survival rates of CRC in the early-stage and advanced-stage in males and females are approximately 63%–92% and 11%–89%, respectively [4]. It has been reported that the majority of diagnosed CRC patients in Thailand have advanced-stage cancer (70.80%), with an overall survival rate of 5% [4,5]. Previous studies reported that new CRC cases in Thailand increased by 8.68% and 6.86% in males and females, respectively [5,6]. These results indicated that an effective screening program is necessary for the prevention of CRC in the Thai population [5,7,8]. Accumulation for mutation information related to CRC in the Thai population by screening for colorectal adenoma, which is the precursor lesion for CRC, and diagnosis of early-stage CRC are both very important for CRC prevention [9,10]
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