Abstract Background and Aim The mechanism underlying carcinogenesis and the genomic features of superficial non‐ampullary duodenal epithelial tumors (SNADETs) have not been elucidated in detail. In this study, we examined the genomic features of incipient SNADETs, such as small lesions resected via endoscopic treatment, using next‐generation sequencing (NGS). Methods Twenty consecutive patients who underwent endoscopic treatment for SNADETs of less than 20 mm between January and December 2017 were enrolled. Targeted genomic sequencing was performed through NGS using a panel of 160 cancer‐related genes. Furthermore, the alteration/mutation frequencies in SNADETs were examined. Results The maximum size of the SNADETs examined in this study was 12 mm in diameter. Five SNADETs were classified as low‐grade dysplasia (LGD) tumors, while 14 SNADETs were classified as high‐grade dysplasia tumors. Only one carcinoma in situ was detected. NGS data for 16 samples were obtained. APC alterations were detected in 81% of samples (13/16). KRAS, BRAF, and TP53 alterations were detected in 25% (4/16), 18.8% (3/16), and 6.3% (1/16) of cases, respectively. Conclusion We detected APC alterations in most small SNADETs resected via endoscopic treatment, from LGD to carcinoma samples. Even in SNADETs classified as small LGD exhibited KRAS and BRAF alterations.
