Abstract
BackgroundPrecision 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.MethodWe 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.ResultsNineteen 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.ConclusionsWe 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.
Highlights
Precision therapy for lung cancer requires comprehensive genomic analyses
A comparison with the Cancer Genome Atlas dataset showed that epidermal growth factor receptor (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 identified new mutations in ARID1A, ARID2, CDK12, CHEK2, GNAS, H3F3A, KDM6A, KMT2C, NOTCH1, RB1, RBM10, RUNX1, SETD2, SF3B1, SMARCA4, THRAP3, TP53, and ZMYM2
Summary
Precision therapy for lung cancer requires comprehensive genomic analyses. Lung cancer is the leading cause of cancer-associated mortality worldwide. An estimated 2.09 million new lung cancer cases and 1.76 million lung cancer-associated mortalities were reported in the GLOBOCAN 2018 database [1]. Lung cancer can be divided into two broad categories according to histology: small-cell lung cancer and non-small-cell lung cancer (NSCLC). The latter comprises more than 80–85% of all lung cancers. Despite advances in genomic research and targeted therapies, leading to improvements in therapeutic strategies and the clinical outcomes of lung cancer patients [7], the overall 5-year survival rate of lung cancer remains very low (16.8%) [8]. The prognosis of lung cancer remains poor because most patients are often diagnosed at an advanced stage
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