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Sci Rep. 2015 Oct 27;5:14237. doi: 10.1038/srep14237.

Whole Exome Sequencing Identifies Frequent Somatic Mutations in Cell-Cell Adhesion Genes in Chinese Patients with Lung Squamous Cell Carcinoma.

Li C1,2, Gao Z3, Li F4, Li X3,5, Sun Y1,2, Wang M2,6, Li D3, Wang R1,2, Li F4, Fang R4, Pan Y1,2, Luo X1,2, He J2,6, Zheng L3, Xia J4, Qiu L2,6,7, He J3, Ye T1,2, Zhang R2,6, He M3, Zhu M2,6, Hu H1,2, Shi T2,6, Zhou X2,8, Sun M2,8, Tian S3, Zhou Y3, Wang Q3, Chen L3, Yin G3, Lu J3, Wu R3, Guo G3, Li Y3, Hu X3, Li L3, Asan3, Wang Q3, Yin Y3, Feng Q3, Wang B3, Wang H3, Wang M3, Yang X9, Zhang X3, Yang H3, Jin L10, Wang CY11, Ji H4, Chen H1,2, Wang J3,12,13, Wei Q6,14.

Author information

1
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
2
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
3
BGI-Shenzhen, Shenzhen, 518083, China.
4
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Science, Shanghai, 200031, China.
5
Department of Medicine and Therapeutics, State Key Laboratory of Digestive. Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
6
Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
7
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
8
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
9
BGI-Shanghai, Eastern CHINA, BGI-Shenzhen, Shanghai, 201100, China.
10
State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200433, China.
11
Lab of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry and Jonsson Cancer Center, UCLA, Los Angeles, California, 90095, USA.
12
The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200, Denmark.
13
Department of Biology, University of Copenhagen, Copenhagen, 2200, Denmark.
14
Duke Cancer Institute, Duke University Medical Center, and Department of Medicine, Duke University School of Medicine, Durham, North Carolina, 27710, USA.

Abstract

Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy.

PMID:
26503331
PMCID:
PMC4621504
DOI:
10.1038/srep14237
[Indexed for MEDLINE]
Free PMC Article

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