Germline Predisposition and Copy Number Alteration in Pre-stage Lung Adenocarcinomas Presenting as Ground-Glass Nodules
Objective: Synchronous multiple ground-glass nodules (SM-GGNs) are a distinct entity of lung cancer which has been emerging increasingly in recent years in China. The oncogenesis molecular mechanisms of SM-GGNs remain elusive.Methods: We investigated single nucleotide variations (SNV), insertions an...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.00288/full |
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| author | Yijiu Ren Shujun Huang Chenyang Dai Dong Xie Larry Zheng Huikang Xie Hui Zheng Yunlang She Fangyu Zhou Yue Wang Pengpeng Li Ke Fei Gening Jiang Yang Zhang Bo Su E. Alejandro Sweet-Cordero Nhan Le Tran Yanan Yang Jai N. Patel Christian Rolfo Gaetano Rocco Andrés Felipe Cardona Alessandro Tuzi Matteo B. Suter Ping Yang Wayne Xu Wayne Xu Wayne Xu Chang Chen |
| author_facet | Yijiu Ren Shujun Huang Chenyang Dai Dong Xie Larry Zheng Huikang Xie Hui Zheng Yunlang She Fangyu Zhou Yue Wang Pengpeng Li Ke Fei Gening Jiang Yang Zhang Bo Su E. Alejandro Sweet-Cordero Nhan Le Tran Yanan Yang Jai N. Patel Christian Rolfo Gaetano Rocco Andrés Felipe Cardona Alessandro Tuzi Matteo B. Suter Ping Yang Wayne Xu Wayne Xu Wayne Xu Chang Chen |
| author_sort | Yijiu Ren |
| collection | DOAJ |
| description | Objective: Synchronous multiple ground-glass nodules (SM-GGNs) are a distinct entity of lung cancer which has been emerging increasingly in recent years in China. The oncogenesis molecular mechanisms of SM-GGNs remain elusive.Methods: We investigated single nucleotide variations (SNV), insertions and deletions (INDEL), somatic copy number variations (CNV), and germline mutations of 69 SM-GGN samples collected from 31 patients, using target sequencing (TRS) and whole exome sequencing (WES).Results: In the entire cohort, many known driver mutations were found, including EGFR (21.7%), BRAF (14.5%), and KRAS (6%). However, only one out of the 31 patients had the same somatic missense or truncated events within SM-GGNs, indicating the independent origins for almost all of these SM-GGNs. Many germline mutations with a low frequency in the Chinese population, and genes harboring both germline and somatic variations, were discovered in these pre-stage GGNs. These GGNs also bore large segments of copy number gains and/or losses. The CNV segment number tended to be positively correlated with the germline mutations (r = 0.57). The CNV sizes were correlated with the somatic mutations (r = 0.55). A moderate correlation (r = 0.54) was also shown between the somatic and germline mutations.Conclusion: Our data suggests that the precancerous unstable CNVs with potentially predisposing genetic backgrounds may foster the onset of driver mutations and the development of independent SM-GGNs during the local stimulation of mutagens. |
| first_indexed | 2024-12-14T12:44:54Z |
| format | Article |
| id | doaj.art-18253f4f291746699de0076d8a1b7828 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-14T12:44:54Z |
| publishDate | 2019-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-18253f4f291746699de0076d8a1b78282022-12-21T23:00:49ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-04-01910.3389/fonc.2019.00288452975Germline Predisposition and Copy Number Alteration in Pre-stage Lung Adenocarcinomas Presenting as Ground-Glass NodulesYijiu Ren0Shujun Huang1Chenyang Dai2Dong Xie3Larry Zheng4Huikang Xie5Hui Zheng6Yunlang She7Fangyu Zhou8Yue Wang9Pengpeng Li10Ke Fei11Gening Jiang12Yang Zhang13Bo Su14E. Alejandro Sweet-Cordero15Nhan Le Tran16Yanan Yang17Jai N. Patel18Christian Rolfo19Gaetano Rocco20Andrés Felipe Cardona21Alessandro Tuzi22Matteo B. Suter23Ping Yang24Wayne Xu25Wayne Xu26Wayne Xu27Chang Chen28Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, ChinaResearch Institute of Oncology and Hematology, CancerCare Manitoba, Winnipeg, MB, CanadaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, ChinaResearch Institute of Oncology and Hematology, CancerCare Manitoba, Winnipeg, MB, CanadaDepartment of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, ChinaNovogene Bioinformatics Technology Institute, Beijing, ChinaNovogene Bioinformatics Technology Institute, Beijing, ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, ChinaResearch Institute of Oncology and Hematology, CancerCare Manitoba, Winnipeg, MB, CanadaLaboratory center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, ChinaDivision of Hematology and Oncology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, United StatesDepartments of Cancer Biology, Mayo Clinic Arizona, Scottsdale, AZ, United StatesThoracic Disease Research Unit, Division of Pulmonary and Critical Care Medicine, Developmental Therapeutics and Cell Biology Programs, Department of Biochemistry and Molecular Biology, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, MN, United StatesDivision of Hematology/Oncology, Department of Cancer Pharmacology, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, United States0Thoracic Medical Oncology, Experimental Therapeutics Research Program, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, United States1Thoracic Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York City, NY, United States2Thoracic Oncology Unit, Clinical and Translational Oncology Group, Clínica del Country, Bogotá, Colombia3Medical Oncology, ASST Sette Laghi, Varese, Italy3Medical Oncology, ASST Sette Laghi, Varese, Italy4Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United StatesResearch Institute of Oncology and Hematology, CancerCare Manitoba, Winnipeg, MB, Canada5College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada6Department of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, CanadaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, ChinaObjective: Synchronous multiple ground-glass nodules (SM-GGNs) are a distinct entity of lung cancer which has been emerging increasingly in recent years in China. The oncogenesis molecular mechanisms of SM-GGNs remain elusive.Methods: We investigated single nucleotide variations (SNV), insertions and deletions (INDEL), somatic copy number variations (CNV), and germline mutations of 69 SM-GGN samples collected from 31 patients, using target sequencing (TRS) and whole exome sequencing (WES).Results: In the entire cohort, many known driver mutations were found, including EGFR (21.7%), BRAF (14.5%), and KRAS (6%). However, only one out of the 31 patients had the same somatic missense or truncated events within SM-GGNs, indicating the independent origins for almost all of these SM-GGNs. Many germline mutations with a low frequency in the Chinese population, and genes harboring both germline and somatic variations, were discovered in these pre-stage GGNs. These GGNs also bore large segments of copy number gains and/or losses. The CNV segment number tended to be positively correlated with the germline mutations (r = 0.57). The CNV sizes were correlated with the somatic mutations (r = 0.55). A moderate correlation (r = 0.54) was also shown between the somatic and germline mutations.Conclusion: Our data suggests that the precancerous unstable CNVs with potentially predisposing genetic backgrounds may foster the onset of driver mutations and the development of independent SM-GGNs during the local stimulation of mutagens.https://www.frontiersin.org/article/10.3389/fonc.2019.00288/fulllung cancerground-glass nodulewhole-exome sequencingcopy number variationdriver mutations |
| spellingShingle | Yijiu Ren Shujun Huang Chenyang Dai Dong Xie Larry Zheng Huikang Xie Hui Zheng Yunlang She Fangyu Zhou Yue Wang Pengpeng Li Ke Fei Gening Jiang Yang Zhang Bo Su E. Alejandro Sweet-Cordero Nhan Le Tran Yanan Yang Jai N. Patel Christian Rolfo Gaetano Rocco Andrés Felipe Cardona Alessandro Tuzi Matteo B. Suter Ping Yang Wayne Xu Wayne Xu Wayne Xu Chang Chen Germline Predisposition and Copy Number Alteration in Pre-stage Lung Adenocarcinomas Presenting as Ground-Glass Nodules Frontiers in Oncology lung cancer ground-glass nodule whole-exome sequencing copy number variation driver mutations |
| title | Germline Predisposition and Copy Number Alteration in Pre-stage Lung Adenocarcinomas Presenting as Ground-Glass Nodules |
| title_full | Germline Predisposition and Copy Number Alteration in Pre-stage Lung Adenocarcinomas Presenting as Ground-Glass Nodules |
| title_fullStr | Germline Predisposition and Copy Number Alteration in Pre-stage Lung Adenocarcinomas Presenting as Ground-Glass Nodules |
| title_full_unstemmed | Germline Predisposition and Copy Number Alteration in Pre-stage Lung Adenocarcinomas Presenting as Ground-Glass Nodules |
| title_short | Germline Predisposition and Copy Number Alteration in Pre-stage Lung Adenocarcinomas Presenting as Ground-Glass Nodules |
| title_sort | germline predisposition and copy number alteration in pre stage lung adenocarcinomas presenting as ground glass nodules |
| topic | lung cancer ground-glass nodule whole-exome sequencing copy number variation driver mutations |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.00288/full |
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