Relationship between gene mutations and clinicopathological features in nonampullary duodenal epithelial tumors

概要

Background: The pathogenesis of nonampullary duodenal epithelial tumors (NADETs) at the molecular level remains unknown. The aim of this study is to determine the association between the genetic features and clinicopathological findings of NADETs.

Methods: In total, 75 NADETs were enrolled in this study, and we performed targeted DNA sequencing of the GNAS, KRAS, TP53, and APC genes. Histological grade was classified as category 3 or category 4/5 according to the Vienna classification, and the immunophenotype was categorized as the gastric phenotype (G type), gastrointestinal phenotype (GI type), or the intestinal phenotype (I type).

Results: Of the 75 NADETs, GNAS, KRAS, TP53, and APC mutations were detected in 5 (6.7%), 9 (12%), 37 (51.4%), and 66 lesions (88%), respectively. Of the 66 NADETs with APC mutations, 53 lesions had c.4479 G>A synonymous mutation in APC, and other APC mutations were observed in 25 lesions (33.3%). The prevalence of GNAS and KRAS mutations was significantly higher in the G type than in the GI/I type (GNAS, P = 0.027; KRAS, P = 0.005). In contrast, the frequency of TP53 mutations was significantly higher in the GI/I type than in the G type (P = 0.049). Notably, APC mutations, excluding c.4479 G>A, were more frequently identified in category 4/5 tumors than in category 3 tumors (50% vs. 24.5%; P = 0.039).

Conclusion: G-type NADETs harbor frequent GNAS and KRAS mutations, whereas TP53 mutations are common in NADETs with intestinal features. APC mutations were significantly associated with high-grade neoplasia and invasive carcinoma.

この論文で使われている画像