Gene panel testing detects important genetic alterations in ulcerative colitis‑associated colorectal neoplasia

Shimada,Yoshifumi; Shimada,Yoshifumi; Nakano,Mae; Nakano,Mae; Mizuno,Ken-Ichi; Mizuno,Ken-Ichi; Yokoyama,Junji; Yokoyama,Junji; Matsumoto,Akio; Matsumoto,Akio; Tanaka,Kana; Tanaka,Kana; Oyanagi,Hidehito; Oyanagi,Hidehito; Nakano,Masato; Nakano,Masato; Hirose,Yuki; Hirose,Yuki; Ichikawa,Hiroshi; Ichikawa,Hiroshi; Sakata,Jun; Sakata,Jun; Kameyama,Hitoshi; Kameyama,Hitoshi; Takii,Yasumasa; Takii,Yasumasa; Sugai,Mika; Sugai,Mika; Ling,Yiwei; Ling,Yiwei; Takeuchi,Shiho; Takeuchi,Shiho; Okuda,Shujiro; Okuda,Shujiro; Terai,Shuji; Terai,Shuji; Ajioka,Yoichi; Ajioka,Yoichi; Wakai,Toshifumi; Wakai,Toshifumi

doi:10.3892/ol.2022.13562

Gene panel testing detects important genetic alterations in ulcerative colitis‑associated colorectal neoplasia

Authors:
- Yoshifumi Shimada
- Mae Nakano
- Ken-Ichi Mizuno
- Junji Yokoyama
- Akio Matsumoto
- Kana Tanaka
- Hidehito Oyanagi
- Masato Nakano
- Yuki Hirose
- Hiroshi Ichikawa
- Jun Sakata
- Hitoshi Kameyama
- Yasumasa Takii
- Mika Sugai
- Yiwei Ling
- Shiho Takeuchi
- Shujiro Okuda
- Shuji Terai
- Yoichi Ajioka
- Toshifumi Wakai
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Affiliations: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Niigata 951‑8510, Japan, Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Niigata 951‑8510, Japan, Department of Digestive Surgery, Niigata City General Hospital, Niigata, Niigata 950‑1197, Japan, Department of Surgery, Niigata Cancer Center Hospital, Niigata, Niigata 951‑8566, Japan, Division of Medical Technology, Niigata University Graduate School of Health Sciences, Niigata, Niigata 951‑8518, Japan, Medical AI Center/Bioinformatics Laboratory, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Niigata 951‑8514, Japan, Division of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata, Niigata 951‑8510, Japan
Published online on: October 25, 2022 https://doi.org/10.3892/ol.2022.13562
Article Number: 442
Copyright: © Shimada et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ulcerative colitis‑associated neoplasia (UCAN) harbors unique genetic alterations and mutational tendencies. The clinical application of gene panel testing enables precision medicine by tailoring treatment to individual gene alterations. We hypothesized that gene panel testing may detect clinically important genetic alterations in UCAN, with potential usefulness for the diagnosis and treatment of UCAN. In the present study, gene panel testing was used to identify genetic alterations in UCAN, and the possibility of clinical utility of gene panel testing in UCAN was investigated. The present study included 15 patients with UCAN, and gene panel testing was performed to identify genetic alterations associated with diagnosis and treatment. Genetic alterations of UCAN were compared with those of 203 patients with sporadic colorectal cancer (CRC). APC and PTEN mutations were less frequent, while RNF43 frameshift or nonsense mutations were more frequent in UCAN compared with sporadic CRC. TP53 mutations were identified in 13/15 patients (87%) with UCAN. Notably, 4/15 patients (27%) with UCAN had no genetic alterations other than TP53 mutation, while this occurred in 1/203 patients (0.5%) with sporadic CRC (P<0.001). Microsatellite instability‑high was identified in 2/15 patients (13%) with UCAN. Mutational signature 3, which is associated with homologous recombination deficiency, was detected in 14/15 patients (93%) with UCAN, and enriched in UCAN compared with sporadic CRC (P=0.030). In conclusion, gene panel testing can detect important genetic alterations that can be useful for diagnosis and treatment in UCAN, and may provide clinicians with important information for tailored treatment strategies.

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