Druggable driver gene alterations in redefined large cell carcinoma in Chinese patients: an observational study.
Druggable driver gene alterations in redefined large cell carcinoma in Chinese patients: an observational study.
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中国患者重新定义的大细胞癌中可药物驱动基因的改变：一项观察性研究
DOI：
10.21037/tcr-20-1675
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发表时间：
2020-12
影响因子：
0.9
通讯作者：
He W
中科院分区：
文献类型：
--
作者：
Yang J;Li Y;Ma B;Xie H;Chen L;Gao X;He W
根据2015年世界卫生组织（WHO）分类，很少有报道调查中国患者大细胞癌（LCC）的遗传状态。我们的目的是分析药物驱动基因改变的分布，包括表皮生长因子受体（EGFR）、Kirsten大鼠肉瘤2病毒癌基因同源物（KRAS）、原癌基因B-Raf（BRAF）和磷脂酰肌醇-4的突变，棘皮动物微管相关蛋白样4-间变性淋巴瘤激酶5-磷酸氢盐3-激酶催化亚基α（PIK3CA）和易位在2015年WHO分类下的大规模LCC患者人群中检测EML 4-ALK和ROS原癌基因1（ROS 1），并评估携带这些遗传改变的LCC患者的临床结局。方法回顾性分析2015年6月至2018年12月期间322例LCC患者的临床资料。回顾性收集患者的临床特征和EGFR、KRAS、BRAF、PIK3CA、EML 4-ALK和ROS 1改变的分布数据。采用log-rank检验分析LCC患者的无病生存期（DFS）。结果在重新定义的LCC患者中，男性比例明显高于女性。LCC的检测在> 60岁的患者中更常见（71.4%）。在3.6%的LCC参与者中发现了EGFR突变，主要是在非吸烟者中。在7.8%的LCC患者中观察到KRAS突变，主要发生在男性和吸烟者中。PIK3CA和EML4-ALK易位中的突变分别占已确定改变的2.1%和0.52%。在ROS1和BRAF中未发现改变。分子分层后，野生型（WT）和突变组之间的DFS无显著差异（29.91 ± 3.83 vs. 25.33 ± 6.04个月，P = 0.48）。结论根据2015年WHO标准，LCC在老年男性下丘脑患者中更常见。EGFR和KRAS突变的频率最高。EGFR突变在非吸烟者中更常见，而KRAS突变主要发生在男性和吸烟者中。PIK3CA突变和EML4-ALK易位在LCC患者中罕见。我们的数据显示，在LCC中识别临床上可操作的分子改变可能有助于指导未来的个性化癌症治疗决策。
Background Few reports have investigated the genetic status of large cell carcinoma (LCC) in Chinese patients under the 2015 World Health Organization (WHO) classification. We aimed to analyze the distribution of druggable driver gene alterations, including mutations in epidermal growth factor receptor (EGFR), Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), proto-oncogene B-Raf (BRAF), and phosphatidylinositol-4,5 biphosphate 3-kinase catalytic subunit alpha (PIK3CA) and translocations in echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) and ROS proto-oncogene 1 (ROS1), in a large population of patients with LCC under the 2015 WHO classification, and to assess the clinical outcomes of patients with LCC harboring these genetic alterations. Methods A cohort of 322 patients with LCC resected between June 2015 and December 2018 was included in this study. The clinical characteristics of the patients and data on the distribution of EGFR, KRAS, BRAF, PIK3CA, EML4-ALK, and ROS1 alterations were retrospectively collected. The disease-free survival (DFS) of patients with LCC was analyzed using the log-rank test. Results Among the patients with redefined LCC, the proportion of males was much higher than that of females. Detection of LCC was more frequent in patients >60 years of age (71.4%). Mutations of EGFR were found in 3.6% of the LCC participants, predominantly in non-smokers. Mutations in KRAS were observed in 7.8% of the LCC patients, mainly in males and smokers. Mutations in PIK3CA and EML4-ALK translocations comprised 2.1% and 0.52% of the identified alterations, respectively. No alterations were identified in ROS1 and BRAF. After molecular stratification, no significant difference in DFS was identified between wild-type (WT) and mutation groups (29.91±3.83 vs. 25.33±6.04 months, P=0.48). Conclusions Under the 2015 WHO criteria, LCC was more frequently detected in elderly male patients with inferior prognoses. The frequency of EGFR and KRAS mutations was found to be the highest. Mutations in EGFR occurred more frequently in non-smokers, whereas KRAS mutations occurred predominantly in males and smokers. The PIK3CA mutations and EML4-ALK translocations were rare in patients with LCC. Our data revealed that the identification of clinically actionable molecular alterations in LCC may help guide personalized cancer treatment decisions in the future.
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影响因子：
11.2
作者：
Yamamoto H;Shigematsu H;Nomura M;Lockwood WW;Sato M;Okumura N;Soh J;Suzuki M;Wistuba II;Fong KM;Lee H;Toyooka S;Date H;Lam WL;Minna JD;Gazdar AF
通讯作者：
Gazdar AF
影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
DOI：
10.1093/annonc/mdt205
发表时间：
2013-09
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Dearden S;Stevens J;Wu YL;Blowers D
通讯作者：
Blowers D
影响因子：
45.3
作者：
Scagliotti, Giorgio Vittorio;Parikh, Purvish;Gandara, David
通讯作者：
Gandara, David
影响因子：
158.5
作者：
Sandler, Alan;Gray, Robert;Johnson, David H.
通讯作者：
Johnson, David H.