Mutation profile of non-small cell lung cancer revealed by next generation sequencing

• Published in: Respiratory research Vol. 22; no. 1; pp. 3 - 10
• Main Authors: Chang, Ya-Sian, Tu, Siang-Jyun, Chen, Yu-Chia, Liu, Ting-Yuan, Lee, Ya-Ting, Yen, Ju-Chen, Fang, Hsin-Yuan, Chang, Jan-Gowth
• Format: Journal Article
• Language: English
• Published: London BioMed Central 06.01.2021; BioMed Central Ltd; Nature Publishing Group; BMC
• Subjects: Adenocarcinoma; Cancer; Care and treatment; Cell cycle; Data analysis; Deoxyribonucleic acid; Development and progression; DNA; DNA polymerase; DNA repair; Epidermal growth factor receptors; Epigenetics; Gene expression; Gene mutations; Gene sequencing; Genetic aspects; Genomes; Genomic analysis; Kinases; Lung cancer; Lung cancer, Non-small cell; Medical prognosis; Medical screening; Medicine; Medicine & Public Health; Mutation; Next-generation sequencing; Non-small cell lung cancer; Non-small cell lung carcinoma; Notch1 protein; Oncology, Experimental; p53 Protein; Pneumology/Respiratory System; Populations; Ribonucleic acid; RNA; RNA sequencing; Runx1 protein; Small cell lung carcinoma; Software; Squamous cell carcinoma; Survival analysis; Targeted gene sequencing; Trunk mutations; Tumorigenesis; Tumors; Whole-exome sequencing; Taiwan; United States > US; Germany; Targeted gene sequencing; Whole-exome sequencing; Trunk mutations; Non-small cell lung cancer
• ISSN: 1465-993X; 1465-9921; 1465-993X
• DOI: 10.1186/s12931-020-01608-5

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. Method 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.