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Gene. 2018 Jan 30;641:94-104. doi: 10.1016/j.gene.2017.10.020. Epub 2017 Oct 17.

Characterization of germline mutations in familial lung cancer from the Chinese population.

Author information

1
Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Kunming College of Life Sciences, University of Chinese Academy of Sciences, Kunming, China.
2
Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
3
Computational Biology and Medical Ecology Laboratory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
4
Department of Thoracic Surgery, The First People's Hospital of Yunnan Province, Kunming, China.
5
Department of Thoracic and Cardiovascular Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital), Kunming, China; The International Cooperation Key Laboratory of Regional Tumor in High Altitude Area, Ministry of Education of the People's Republic of China, Kunming, China.
6
Department of Thoracic and Cardiovascular Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital), Kunming, China; The International Cooperation Key Laboratory of Regional Tumor in High Altitude Area, Ministry of Education of the People's Republic of China, Kunming, China. Electronic address: huangych2001@aliyun.com.
7
Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. Electronic address: caoy@mail.kiz.ac.cn.

Abstract

Compared with numerous studies of somatic mutations using sporadic lung cancer, the research into germline mutations using familial lung cancer (FLC) is limited. In the present study, we used FLC samples obtained from the Chinese population in highly air-polluted regions to screen for novel germline mutations in lung cancer. Through a whole genome sequencing (WGS) analysis of the nine subjects (four lung cancer patients and five normal family members of FLC), we obtained a whole genome dataset of DNA alterations in FLC samples. A total of 1218 genes were identified with mutations of multiple types. Subsequently, the top 12 highly mutated genes were selected for validation by polymerase chain reaction and DNA sequencing in an expanded sample set including FLC, sporadic lung cancer, and healthy population. Mutations of the five genes (ARHGEF5, ANKRD20A2, ZNF595, ZNF812, MYO18B) may be potential germline mutations of lung cancer. We also analyzed specific mutations within the 12 genes and found that some specific mutations within the MUC12, FOXD4L3 and FOXD4L5 genes showed higher frequencies in the samples of FLC and/or lung cancer tissue, compared with the healthy population. Moreover, some genes with copy number variation may be potentially associated with a predisposition to lung cancer. Furthermore, non-coding DNA alterations of the WGS data in FLC were systematically analyzed and arranged. Interestingly, we found that germline mutations also occurred in many genes of non-coding RNA. This study uncovered the mutation spectrum in FLC and provided important clues for the evaluation of the genetic susceptibility to lung cancer.

KEYWORDS:

Air pollution; Chinese population; Familial lung cancer; Genetic predisposition; Germline mutation; Whole genome sequencing

PMID:
29054765
DOI:
10.1016/j.gene.2017.10.020
[Indexed for MEDLINE]

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