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Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：肺癌的精确治疗需要全面的基因组分析。在亚洲人群中已经报道了靶向治疗的具体效果，包括台湾人,但是在这些人群中很少进行基因组研究。
方法：我们招募了72例非小细胞肺癌患者，其中61人患有腺癌，10人患有鳞状细胞癌，1例合并腺癌和鳞状细胞癌。进行全外显子组或靶向基因测序。为了识别躯干突变，我们对4例患者的2个肿瘤区域进行了全外显子组测序.
结果：19个已知的EGFR驱动突变，PIK3CA,KRAS,CTNNB1和MET在评估的72个肿瘤中的34个中被鉴定(47.22%)。与癌症基因组图谱数据集的比较表明，EGFR在我们的队列中突变的频率远高于高加索人，而KRAS和TP53突变仅在我们的5.56%和25%的台湾患者中发现，分别。我们还发现了ARID1A的新突变，ARID2,CDK12,CHEK2,GNAS,H3F3A,KDM6A,KMT2C,NOTCH1、RB1、RBM10、RUNX1、SETD2、SF3B1、SMARCA4、THRAP3、TP53和ZMYM2。此外，所有ClinVar致病变异体均为存在于肿瘤两个区域的主干突变.RNA测序显示，主干或分支基因在不同肿瘤区域中以相似的水平表达。
结论：我们发现了可能与肺癌肿瘤发生相关的新变异。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。
方法：我们招募了72例非小细胞肺癌患者，其中61人患有腺癌，10人患有鳞状细胞癌，1例合并腺癌和鳞状细胞癌。进行全外显子组或靶向基因测序。为了识别躯干突变，我们对4例患者的2个肿瘤区域进行了全外显子组测序.
结果：19个已知的EGFR驱动突变，PIK3CA,KRAS,CTNNB1和MET在评估的72个肿瘤中的34个中被鉴定(47.22%)。与癌症基因组图谱数据集的比较表明，EGFR在我们的队列中突变的频率远高于高加索人，而KRAS和TP53突变仅在我们的5.56%和25%的台湾患者中发现，分别。我们还发现了ARID1A的新突变，ARID2,CDK12,CHEK2,GNAS,H3F3A,KDM6A,KMT2C,NOTCH1、RB1、RBM10、RUNX1、SETD2、SF3B1、SMARCA4、THRAP3、TP53和ZMYM2。此外，所有ClinVar致病变异体均为存在于肿瘤两个区域的主干突变.RNA测序显示，主干或分支基因在不同肿瘤区域中以相似的水平表达。
结论：我们发现了可能与肺癌肿瘤发生相关的新变异。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。
