The log R ratio (LRR) and B allele frequency (BAF) for each sample were exported from normalized Illumina data using GenomeStudio. performed. Ninetytwo CRCs were classified into 71 MSS and 21 MSI phenotypes. We examined 71 CRCs with the MSS phenotype (LC, 56; RC, 15). Mutations inKRASwere associated with RC with the MSS phenotype, whereas mutations inTP53were more frequently found in LC with the MSS phenotype. There were significant differences in the frequencies ofKRASandTP53mutations in the IME between LC and RC with the MSS phenotype. Although CNA gains were associated with LC with the MSS phenotype, CNA losses were not major alterations associated with the MSS phenotype. These findings suggested that the molecular pathogenesis of the MSS phenotype in LC was different from that in RC. Keywords: colorectal cancer, copy number modification, microsatellite stable, mutation, tumor location == Short subjective == What’s new? The classification of colorectal cancer (CRC) based on tumor location is simple, comprehensive, and consistent with recent attempts to characterize tumors by pathological and molecular features. Differences in the pathogenesis of microsatellite stable (MSS) sporadic CRCs between leftsided CRC (LC) and rightsided CRC (RC) Naringin Dihydrochalcone (Naringin DC) have however not been clarified. Here, the authors found thatTP53mutations are closely associated with the development of LC whereas RC is characterized byKRASmutations. Using an integrated genomewide analysis, they also show significant differences in copy number alterations. The findings suggest a different molecular pathogenesis of the MSS phenotype between LC and RC. Colorectal cancer (CRC) is a major cause of morbidity and mortality throughout the world. 1It is the third most common cancer worldwide and the fourth most common cause of death. 1Therefore, CRC is one of the most HOX1I important cancers in the world. 1, 2The prognosis of patients with CRC has improved owing to recent advances in Naringin Dihydrochalcone (Naringin DC) technology, and further improvements in our understanding of the pathological and molecular basis of disease have contributed to potential new approaches for the diagnosis and treatment of CRC. Therefore , it is important to continue to evaluate the role of molecular alterations in colorectal carcinogenesis. Genomic instability plays an essential role in the development and progression of CRC. 3, 4, 5Based on different forms of genomic instability, sporadic CRC can broadly be divided into two groups: the microsatellite instability (MIN; MSI) type, caused by MLH1 methylation of the promoter region, and the chromosome instability (CIN) type, characterized by genomic instability at the gross chromosomal level. 3, 4, 5The majority of sporadic CRCs (90%) are classified into the CIN type, whereas only approximately 10% of sporadic CRCs are classified into the MIN type. 3, 4, 5, 6, 7In addition, the microsatellite stable (MSS) type, which is similar to CIN, is also important in colorectal carcinogenesis. Studies have shown that MSI and MSS are mutually exclusive and are also used as basic molecular classification. a few, 7 CRCs that occur proximal (right) or distal (left) to the splenic flexure exhibit differences in their embryologic development, blood supply and clinicopathological findings. 8, 9, 10, 11, 12A previous study showed that classification based on tumor location, that is, leftsided CRC (LC) and rightsided CRC (RC), is also useful and essential for understanding colorectal carcinogenesis. 8, 9Although CRC with the MSIhigh phenotype preferentially occurs in the rightsided colon, it is rarely found in the leftsided colon. 8, 9However, the MSS phenotype is the main molecular phenotype in both LC and RC. 10, 11Previous Naringin Dihydrochalcone (Naringin DC) Naringin Dihydrochalcone (Naringin DC) reports have shown that the MSS phenotype is found in approximately 6070% of RC and around 90% of LC. 3, 7To identify the molecular or clinicopathological differences between LC and RC, we must analyze the molecular or clinicopathological differences in the MSS phenotype between LC and RC, given that the MSS phenotype is common in CRC. In the current study, we aimed to validate the molecular profiles of MSS CRC based on tumor location. == Material and Methods == == Patients == Tumor specimens were obtained from 92 patients who had undergone colectomy at Iwate Medical University Hospital (Iwate, Japan) between 2013 and 2015. Clinicopathological findings, including age, sex,.