Mutation profile of non-small cell lung cancer revealed by next generation sequencing
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. Method We enrolled 72 patients with...
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| Format: | Article |
| Language: | English |
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BMC
2021-01-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-020-01608-5 |
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| author | Ya-Sian Chang Siang-Jyun Tu Yu-Chia Chen Ting-Yuan Liu Ya-Ting Lee Ju-Chen Yen Hsin-Yuan Fang Jan-Gowth Chang |
| author_facet | Ya-Sian Chang Siang-Jyun Tu Yu-Chia Chen Ting-Yuan Liu Ya-Ting Lee Ju-Chen Yen Hsin-Yuan Fang Jan-Gowth Chang |
| author_sort | Ya-Sian Chang |
| collection | DOAJ |
| description | 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. 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. |
| first_indexed | 2024-12-16T07:12:26Z |
| format | Article |
| id | doaj.art-6d30577c67d541899be54264480876c6 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-12-16T07:12:26Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-6d30577c67d541899be54264480876c62022-12-21T22:39:51ZengBMCRespiratory Research1465-993X2021-01-0122111010.1186/s12931-020-01608-5Mutation profile of non-small cell lung cancer revealed by next generation sequencingYa-Sian Chang0Siang-Jyun Tu1Yu-Chia Chen2Ting-Yuan Liu3Ya-Ting Lee4Ju-Chen Yen5Hsin-Yuan Fang6Jan-Gowth Chang7Epigenome Research Center, China Medical University HospitalDepartment of Laboratory Medicine, China Medical University HospitalCenter for Precision Medicine, China Medical University HospitalCenter for Precision Medicine, China Medical University HospitalEpigenome Research Center, China Medical University HospitalEpigenome Research Center, China Medical University HospitalDepartment of Thoracic Surgery, China Medical University HospitalEpigenome Research Center, China Medical University HospitalAbstract 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.https://doi.org/10.1186/s12931-020-01608-5Non-small cell lung cancerWhole-exome sequencingTargeted gene sequencingTrunk mutations |
| spellingShingle | Ya-Sian Chang Siang-Jyun Tu Yu-Chia Chen Ting-Yuan Liu Ya-Ting Lee Ju-Chen Yen Hsin-Yuan Fang Jan-Gowth Chang Mutation profile of non-small cell lung cancer revealed by next generation sequencing Respiratory Research Non-small cell lung cancer Whole-exome sequencing Targeted gene sequencing Trunk mutations |
| title | Mutation profile of non-small cell lung cancer revealed by next generation sequencing |
| title_full | Mutation profile of non-small cell lung cancer revealed by next generation sequencing |
| title_fullStr | Mutation profile of non-small cell lung cancer revealed by next generation sequencing |
| title_full_unstemmed | Mutation profile of non-small cell lung cancer revealed by next generation sequencing |
| title_short | Mutation profile of non-small cell lung cancer revealed by next generation sequencing |
| title_sort | mutation profile of non small cell lung cancer revealed by next generation sequencing |
| topic | Non-small cell lung cancer Whole-exome sequencing Targeted gene sequencing Trunk mutations |
| url | https://doi.org/10.1186/s12931-020-01608-5 |
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