Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea.
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Sci Rep. 2021 Oct 1;11(1):19596. doi: 10.1038/s41598-021-99197-w.
Recurrent gene mutations and fusions in cancer patients are likely to be associated with cancer progression or recurrence by Vogelstein et al. (Science (80-) 340, 1546-1558 (2013)). In this study, we investigated gene mutations and fusions that recurrently occurred in early-stage cancer patients with stage I non-small-cell cancer (NSCLC). Targeted exome sequencing was performed to profile the variants and confirmed their fidelity at the gene and pathway levels through comparison with data for stage I lung cancer patients, which was obtained from The Cancer Genome Atlas (TCGA). Next, we identified prognostic gene mutations (ATR, ERBB3, KDR, and MUC6), fusions (GOPC-ROS1 and NTRK1-SH2D2A), and VEGF signaling pathway associated with cancer recurrence. To infer the functional implication of the recurrent variants in early-stage cancers, the extent of their selection pattern was investigated, and they were shown to be under positive selection, implying a selective advantage for cancer progression. Specifically, high selection scores were observed in the variants with significantly high risks for recurrence. Taken together, the results of this study enabled us to identify recurrent gene mutations and fusions in a stage I NSCLC cohort and to demonstrate positive selection, which had implications regarding cancer recurrence.
癌症患者中反复出现的基因突变和融合可能与癌症的进展或复发有关，这是由 Vogelstein 等人提出的。在这项研究中，我们研究了在 I 期非小细胞肺癌（NSCLC）的早期癌症患者中反复发生的基因突变和融合。通过靶向外显子组测序来分析这些变体，并通过与癌症基因组图谱（TCGA）中 I 期肺癌患者的数据进行比较，在基因和途径水平上确认其保真度。接下来，我们鉴定了与癌症复发相关的预后基因突变（ATR、ERBB3、KDR 和 MUC6）、融合（GOPC-ROS1 和 NTRK1-SH2D2A）和 VEGF 信号通路。为了推断这些反复出现的变体在早期癌症中的功能意义，我们研究了它们选择模式的程度，并发现它们受到正选择的影响，这意味着它们对癌症进展具有选择性优势。具体来说，在与复发风险显著相关的变体中观察到较高的选择评分。总之，这项研究的结果使我们能够在 I 期 NSCLC 队列中识别出反复出现的基因突变和融合，并证明了正选择，这对癌症复发具有重要意义。
