Epigenome Research Center, China Medical University Hospital, 2 Yuh-Der Road, Taichung, 404, Taiwan.
Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan.
Respir Res. 2021 Jan 6;22(1):3. doi: 10.1186/s12931-020-01608-5.
Precision therapy for lung cancer requires comprehensive genomic analyses. Specific effects of targeted therapies have been reported in Asia populations, including Taiwanese, but genomic studies have rarely been performed in these populations.
We enrolled 72 patients with non-small cell lung cancer, of whom 61 had adenocarcinoma, 10 had squamous cell carcinoma, and 1 had combined adenocarcinoma and squamous cell carcinoma. Whole-exome or targeted gene sequencing was performed. To identify trunk mutations, we performed whole-exome sequencing in two tumor regions in four patients.
Nineteen known driver mutations in EGFR, PIK3CA, KRAS, CTNNB1, and MET were identified in 34 of the 72 tumors evaluated (47.22%). A comparison with the Cancer Genome Atlas dataset showed that EGFR was mutated at a much higher frequency in our cohort than in Caucasians, whereas KRAS and TP53 mutations were found in only 5.56% and 25% of our Taiwanese patients, respectively. We also identified new mutations in ARID1A, ARID2, CDK12, CHEK2, GNAS, H3F3A, KDM6A, KMT2C, NOTCH1, RB1, RBM10, RUNX1, SETD2, SF3B1, SMARCA4, THRAP3, TP53, and ZMYM2. Moreover, all ClinVar pathogenic variants were trunk mutations present in two regions of a tumor. RNA sequencing revealed that the trunk or branch genes were expressed at similar levels among different tumor regions.
We identified novel variants potentially associated with lung cancer tumorigenesis. The specific mutation pattern in Taiwanese patients with non-small cell lung cancer may influence targeted therapies.
肺癌的精准治疗需要全面的基因组分析。针对亚洲人群（包括台湾地区）的靶向治疗已有相关特定疗效的报道，但这些人群的基因组研究却很少进行。
我们纳入了 72 例非小细胞肺癌患者，其中 61 例为腺癌，10 例为鳞状细胞癌，1 例为腺癌和鳞状细胞癌混合癌。对所有患者进行了全外显子或靶向基因测序。为了鉴定主干突变，我们对 4 例患者的两个肿瘤区域进行了全外显子测序。
在 72 例可评估肿瘤中，发现了 19 种已知的驱动基因突变，包括 EGFR、PIK3CA、KRAS、CTNNB1 和 MET 中的突变，占 34.0%（72/212）。与癌症基因组图谱（Cancer Genome Atlas，TCGA）数据集的比较显示，我们的研究队列中 EGFR 的突变频率明显高于白种人，而 KRAS 和 TP53 突变在我们的台湾患者中分别仅占 5.56%和 25%。我们还在 ARID1A、ARID2、CDK12、CHEK2、GNAS、H3F3A、KDM6A、KMT2C、NOTCH1、RB1、RBM10、RUNX1、SETG2、SF3B1、SMARCA4、THRAP3、TP53 和 ZMYM2 中鉴定了新的突变。此外，所有 ClinVar 致病性变异均为肿瘤两个区域存在的主干突变。RNA 测序显示，不同肿瘤区域主干或分支基因的表达水平相似。
我们发现了可能与肺癌发生相关的新的变异。台湾非小细胞肺癌患者的特定突变模式可能会影响靶向治疗。
