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小细胞肺癌中的O-甲基鸟嘌呤-DNA甲基转移酶甲基化与异柠檬酸脱氢酶1/2突变

O-methyl-guanine-DNA methyltransferase methylation and IDH1/2 mutation in small cell lung cancer.

作者信息

Lu Hongyang, Qin Jing, Xu Haimiao, Han Na, Xie Fajun, Mao Weimin

机构信息

Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.

Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.

出版信息

Exp Ther Med. 2017 Jul;14(1):398-402. doi: 10.3892/etm.2017.4476. Epub 2017 May 18.

Abstract

Small cell lung cancer (SCLC) is sensitive to first-line chemotherapy and radiotherapy, but frequently recurs. Temozolomide is a chemotherapeutic drug suitable for the treatment of relapsed SCLC, particularly when brain metastases are present. The response of SCLC to temozolomide may be associated with the methylation status of O-methyl-guanine-DNA methyltransferase (MGMT). Isocitrate dehydrogenase (IDH) mutation is an independent prognostic factor of good outcome in gliomas and appears to be a significant marker of positive chemosensitivity in secondary glioblastoma. In order to identify the status of MGMT promoter methylation and IDH1/2 mutation of SCLC in China, 33 SCLC specimens from patients that underwent surgery were retrospectively collected in Zhejiang Cancer Hospital (Hangzhou, China) between 2008 and 2014. High-resolution melting analysis and methylation-specific polymerase chain reaction were used to detect MGMT promoter methylation, and polymerase chain reaction amplification and Sanger sequencing were utilized to detect IDH1/2 mutation. Of the 33 examined SCLC specimens, MGMT promoter methylation was detected in 17 patients (51.5%), and no IDH1/2 mutations were detected in the analyzed samples. These findings indicate that the IDH1/2 mutation may not be an ideal marker in SCLC patients treated with temozolomide. Future studies on the predictive and prognostic value of MGMT promoter methylation are urgently required for patients with relapsed SCLC treated with temozolomide in China.

摘要

小细胞肺癌(SCLC)对一线化疗和放疗敏感,但常复发。替莫唑胺是一种适用于治疗复发性SCLC的化疗药物,尤其是存在脑转移时。SCLC对替莫唑胺的反应可能与O-甲基鸟嘌呤-DNA甲基转移酶(MGMT)的甲基化状态有关。异柠檬酸脱氢酶(IDH)突变是胶质瘤预后良好的独立预测因素,似乎是继发性胶质母细胞瘤化疗敏感性阳性的重要标志物。为了明确中国SCLC患者中MGMT启动子甲基化和IDH1/2突变的状况,2008年至2014年期间,在浙江省肿瘤医院(中国杭州)回顾性收集了33例接受手术治疗的SCLC患者的标本。采用高分辨率熔解分析和甲基化特异性聚合酶链反应检测MGMT启动子甲基化,利用聚合酶链反应扩增和桑格测序检测IDH1/2突变。在33例检测的SCLC标本中,17例患者(51.5%)检测到MGMT启动子甲基化,分析样本中未检测到IDH1/2突变。这些发现表明,IDH1/2突变可能不是接受替莫唑胺治疗的SCLC患者的理想标志物。在中国,对于接受替莫唑胺治疗的复发性SCLC患者,迫切需要进一步研究MGMT启动子甲基化的预测和预后价值。

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