Xie Tongji, Li Yan, Ying Jianming, Cai Weijing, Li Junling, Lee Kye Young, Ricciuti Biagio, Pacheco Jose, Xing Puyuan
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Shanghai Tongshu Biotechnology Co., Ltd, Shanghai, China.
Transl Lung Cancer Res. 2020 Dec;9(6):2428-2439. doi: 10.21037/tlcr-20-1278.
Histologic transformation of non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is a rare mechanism of acquired resistance to epidermal growth factor receptor ()-targeted tyrosine kinase inhibitors. However, the SCLC transformation has also been observed in non.
mutant NSCLC. In these cases, whether SCLC initially co-exists with NSCLC or originates from initial NSCLC remains to be determined.
Whole exome sequencing was performed on 10 samples from 5 patients with SCLC transformation from lung adenocarcinoma (LUAD), a main subtype of NSCLC. Somatic mutations and copy number variations (CNVs) were analyzed to explore the differences between initial LUAD and transformed SCLC, as well as the origin of transformed SCLC.
After SCLC transformation, the mutation spectrum changed, with decreased C>T and increased C>A. Compared with initial LUAD, the CNV burden of transformed SCLC was greatly increased (39.0 . 61.1, Wilcoxon P=0.4). The higher the CNV burden of LUAD, the shorter the time to SCLC transformation was observed to be; and the higher the CNV burden of transformed SCLC, the shorter the overall survival (OS) after transformation. Clonal evolution analysis showed different clonal components between initial LUAD and transformed SCLC.
The transformation of LUAD into SCLC may be promoted by CNV events rather than mutational events. CNV burden was associated with the time to SCLC transformation and with the OS of patients following SCLC transformation. Transformed SCLC did not evolve directly from the initial LUAD but branched off from LUAD before the time of initial diagnosis.
非小细胞肺癌（NSCLC）向小细胞肺癌（SCLC）的组织学转化是一种罕见的获得性表皮生长因子受体（EGFR）靶向酪氨酸激酶抑制剂耐药机制。然而，在非EGFR突变的NSCLC中也观察到了SCLC转化。在这些病例中，SCLC最初是否与NSCLC共存或起源于初始NSCLC仍有待确定。
对5例肺腺癌（LUAD，NSCLC的主要亚型）发生SCLC转化的患者的10个样本进行全外显子测序。分析体细胞突变和拷贝数变异（CNV），以探讨初始LUAD与转化后的SCLC之间的差异，以及转化后SCLC的起源。
SCLC转化后，突变谱发生变化，C>T减少，C>A增加。与初始LUAD相比，转化后SCLC的CNV负担大大增加（39.0对61.1，Wilcoxon P = 0.4）。观察到LUAD的CNV负担越高，SCLC转化的时间越短；转化后SCLC的CNV负担越高，转化后的总生存期（OS）越短。克隆进化分析显示初始LUAD和转化后SCLC之间存在不同的克隆成分。
LUAD向SCLC的转化可能由CNV事件而非突变事件促进。CNV负担与SCLC转化的时间以及SCLC转化后患者的OS相关。转化后的SCLC并非直接从初始LUAD进化而来，而是在初始诊断之前从LUAD分支出来。
