title: Sessile serrated adenoma shares similar genetic and epigenetic features with microsatellite unstable colon cancer in a location-dependent manner.
abstract: Genetic and epigenetic features of sessile serrated adenoma (SSA), a precursor lesion to colon cancer with microsatellite instability (MSI), were investigated. The aim of this study was to clarify whether there are location-dependent genetic and epigenetic features in SSA. Twenty-two patients with proximal SSAs and 8 with distal SSAs were recruited. Twenty-two patients with tubular adenoma (TA) and 66 with proximal colon cancer were studied for comparison. Genetic and epigenetic features were evaluated as BRAF and KRAS mutations, MSI, hMLH1 methylation and CpG island methylator phenotype (CIMP). BRAF mutation (p=0.007) and CIMP (p=0.012) were more frequently found in proximal than in distal SSAs. Furthermore, the KRAS mutation was found only in distal SSAs. In TAs, no location-related molecular features were observed. All SSAs, TAs and 42 colon cancer lesions were microsatellite stable (MSS). Twenty-four colon cancer lesions exhibited MSI and had more frequent BRAF mutations (p<0.001), hMLH1 methylation (p<0.001) and CIMP (p<0.001). BRAF mutation occurred in only 9.5% of MSS cancers (p=0.01). In MSI cancers with the BRAF mutation, a higher correlation with CIMP (p=0.032) was observed. We demonstrated the distinct genetic and epigenetic features between proximal and distal SSAs. Similar genetic and epigenetic features were shared between proximal SSAs and proximal MSI cancers harboring the BRAF mutation. By contrast, our results allow the possibility of carcinogenesis in SSAs leading to MSS cancer with the BRAF mutation.
authors.affiliation: Departments of Surgery.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Maeda
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kazutomo
authors.initials: K
authors.lastname: Togashi
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nokubi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Saito
authors.forename: Shingo
authors.initials: S
authors.lastname: Tsujinaka
authors.forename: Hidenori
authors.initials: H
authors.lastname: Kamiyama
authors.forename: Fumio
authors.initials: F
authors.lastname: Konishi