Comparative study on the mutational profile of adenocarcinoma and squamous cell carcinoma predominant histologic subtypes in Chinese non-small cell lung cancer patients
Comparative study on the mutational profile of adenocarcinoma and squamous cell carcinoma predominant histologic subtypes in Chinese non-small cell lung cancer patients
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中国非小细胞肺癌患者腺癌和鳞癌主要组织学亚型突变谱的比较研究
DOI：
10.1111/1759-7714.13208
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发表时间：
2019-11-06
期刊：
影响因子：
2.9
通讯作者：
Zhang, Zhihong
中科院分区：
文献类型：
--
作者：
Ding, Ying;Zhang, Lihua;Zhang, Zhihong
背景在常见的组织学类型肺腺癌（LUAD）和肺鳞状细胞癌（LUSC）之间的突变谱的区别已经得到了很好的建立。然而，LUAD和LUSC中主要组织学亚型的综合突变谱仍然难以捉摸。方法采用捕获式超深度测序技术，对来自7家医院的318例非小细胞肺癌（NSCLC）患者的68个肺癌相关基因进行突变谱分析。结果318例NSCLC患者中，LUAD 215例，LUSC 103例。原位腺癌和腺泡腺癌是LUAD的主要亚型。另一方面，角化性鳞状细胞癌是LUSC的最主要亚型。在LUAD亚型中，EGFR致敏突变在侵袭性麻风亚型中最常见。超过一半的浸润前原位腺癌、微创腺癌、腺泡腺癌、微乳头腺癌和乳头腺癌亚型患者也是EGFR突变体。胶体型、浸润性粘液型和胎儿型患者EGFR突变数量最少。此外，KRAS突变在浸润性粘液、胶体、肠和固体亚型患者中普遍存在。总共90%的LUSC患者在TP 53中具有突变，其中除了5名非角化患者之外，所有患者都是TP 53突变体。PIK3CA扩增在角化中最普遍，其次是基底细胞样和非角化亚型。结论各主要组织学亚型间的突变谱差异较大，为临床治疗提供了可靠的依据。
Background Distinction in the mutational profile between the common histological types, lung adenocarcinoma (LUAD) and squamous cell lung carcinoma (LUSC) has been well-established. However, comprehensive mutation profiles of the predominant histological subtypes within LUAD and LUSC remains elusive. Methods We analyzed the mutational profile of 318 Chinese NSCLC patients of adenocarcinoma and squamous cell carcinoma predominant subtypes from seven hospitals using capture-based ultra-deep sequencing of 68 lung cancer-related genes. Results Of the 318 NSCLC patients, 215 were diagnosed with LUAD and 103 with LUSC. Adenocarcinoma in situ and acinar adenocarcinoma were the most predominant subtypes of LUAD. On the other hand, keratinizing squamous cell carcinoma was the most predominant subtype of LUSC. Among the LUAD subtypes, EGFR sensitizing mutations were most prevalent in the invasive lepidic subtype. More than half of the patients with preinvasive adenocarcinoma in situ, minimally invasive, acinar, micropapillary and papillary subtypes were also EGFR-mutants. Patients with colloidal, invasive mucinous, and fetal subtypes had the least number of EGFR mutations. Moreover, KRAS mutations were prevalent in patients with invasive mucinous, colloid, enteric and solid subtypes. A total of 90% of the LUSC patients harbor mutations in TP53, wherein all patients except five with nonkeratinizing were TP53 mutants. PIK3CA amplifications were most prevalent in keratinizing, followed by basaloid and nonkeratinizing subtypes. Conclusion These data suggest that the mutational profiles among the predominant histological subtypes were very distinct, which provided a reliable tool to improve treatment decisions.