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
Bioinformatics and Systems Biology Program, School of Bioresources and Technology and School of Information Technology, King Mongkut's University of Technology Thonburi, Bangkok 10150, Thailand.
Bioinformatics Unit for Genomic Analysis, Division of Research and International Relations, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok 10210, Thailand.
Cancers (Basel). 2019 Jul 12;11(7):977. doi: 10.3390/cancers11070977.
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 (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 (), Family With Sequence Similarity 123B (), F-Box And WD Repeat Domain Containing 7 (), Sex-Determining Region Y-Box 9 (), Low-Density Lipoprotein Receptor-Related Protein 5 (), Frizzled Class Receptor 10 (), and AT-Rich Interaction Domain 1A () 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 (), Tumor Protein 53 (), and Ataxia-Telangiectasia Mutated () genes are found in the receptor tyrosine kinase-RAS (RTK-RAS) signaling pathway and p53 signaling pathway, respectively. These results suggest that and 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.
结直肠腺瘤是结直肠癌的前驱病变。在结直肠癌（CRC）患者中，从腺瘤到癌的转变与基因畸变的积累有关。然而，仍缺乏能够筛查腺瘤进展为腺癌的标准。本研究首次尝试鉴定泰国患者中存在的基因畸变，如体细胞突变、拷贝数变异（CNV）和高频突变基因。在本研究中，我们鉴定了两个样本组的基因组异常情况。第一组有5例样本，匹配正常-结直肠腺瘤-结直肠癌。第二组有6例样本，匹配正常-结直肠腺瘤。对两组样本均进行了全外显子组测序。我们比较了两个样本组的基因畸变情况。在正常组织与结直肠腺瘤及结直肠癌的分析中，10例患者中有8例在肿瘤抑制基因（腺瘤性息肉病 coli）中观察到体细胞突变。在正常组织与结直肠腺瘤组织的比较组中，还在连环蛋白β1（）、序列相似性家族123B（）、含F-Box和WD重复结构域7（）、性别决定区Y框9（）、低密度脂蛋白受体相关蛋白5（）、卷曲蛋白家族受体10（）和富含AT相互作用结构域1A（）基因中检测到体细胞突变，这些基因参与无翅相关整合位点（Wnt）信号通路。在正常组织与结直肠腺癌组织的比较中，分别在受体酪氨酸激酶-RAS（RTK-RAS）信号通路和p53信号通路中发现了 Kirsten 逆转录病毒相关DNA序列（）、肿瘤蛋白53（）和共济失调毛细血管扩张突变（）基因。这些结果表明，和可能作为结直肠腺瘤和早期CRC的潜在筛查标志物。这项初步研究可能有助于识别腺瘤和早期CRC患者，并可能有助于制定预防和监测策略以降低CRC的发病率。
