Kim Nah Ihm, Noh Myung-Giun, Kim Jo-Heon, Won Eun Jeong, Lee Yu Jeong, Hur Younghoe, Moon Kyung-Sub, Lee Kyung-Hwa, Lee Jae-Hyuk
Department of Pathology, Chonnam National University Medical School and Hwasun Hospital, Hwasun-gun, South Korea.
Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, South Korea.
Front Oncol. 2020 Aug 18;10:1514. doi: 10.3389/fonc.2020.01514. eCollection 2020.
The molecular profile of cholangiocarcinoma (CC) remains elusive. The prognostic value of isocitrate dehydrogenase (IDH) mutations in CC is controversial, and there have been few relevant studies in Asian populations. In the present study, we investigated the frequency and prognostic significance of IDH mutations in Korean patients with CC. CC specimens were collected from patients who underwent surgical liver resection between 2004 and 2019. Clinical and pathological data were retrospectively reviewed from medical records. Mutational IDH profiling was performed by peptide nucleic acid-mediated PCR clamping in 206 surgical specimens; IDH-mutant samples were confirmed by next-generation sequencing (NGS). Of the 195 patients with CC, six (3.13%) were found to exhibit IDH1 ( = 5) or IDH2 ( = 1) mutations. Among patients with IDH1 mutations, four had R132C (c.394C>T) and one had R132G (c.394C>G) mutations. One patient had R172W (c.514A>T) mutations in IDH2. All IDH-mutant samples were of intrahepatic origin, and patients with IDH mutations had physiological to low serum levels of carbohydrate antigen 19-9 (CA19-9). No association between IDH mutation status and long-term survival outcomes was observed. The frequency of IDH mutations was considerably lower than the 10-20% reported in previous studies. The frequency and pattern of IDH mutations in CC are likely to vary among patients with different ethnicities. These findings suggest that characterization of the oncogenic mutation profile in different populations is of high clinical importance.
胆管癌（CC）的分子特征仍不明确。异柠檬酸脱氢酶（IDH）突变在CC中的预后价值存在争议，且亚洲人群中相关研究较少。在本研究中，我们调查了韩国CC患者中IDH突变的频率及预后意义。CC标本取自2004年至2019年间接受肝切除术的患者。从病历中回顾性分析临床和病理数据。对206份手术标本采用肽核酸介导的PCR钳夹技术进行IDH突变分析；IDH突变样本通过二代测序（NGS）进行确认。在195例CC患者中，发现6例（3.13%）存在IDH1（=5）或IDH2（=1）突变。在IDH1突变患者中，4例有R132C（c.394C>T）突变，1例有R132G（c.394C>G）突变。1例患者IDH2有R172W（c.514A>T）突变。所有IDH突变样本均来自肝内，且IDH突变患者的碳水化合物抗原19-9（CA19-9）血清水平为生理性至低水平。未观察到IDH突变状态与长期生存结果之间存在关联。IDH突变的频率显著低于先前研究报道的10%-20%。CC中IDH突变的频率和模式在不同种族患者中可能存在差异。这些发现表明，不同人群致癌突变谱的特征具有高度临床重要性。
