Whole Exome Sequencing Identifies Frequent Somatic Mutations in Cell-Cell Adhesion Genes in Chinese Patients with Lung Squamous Cell Carcinoma.
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.
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Chenguang
C
Li
BGI-Shenzhen, Shenzhen, 518083, China.
Zhibo
Z
Gao
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Science, Shanghai, 200031, China.
Fei
F
Li
BGI-Shenzhen, Shenzhen, 518083, China.|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.
Xiangchun
X
Li
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Yihua
Y
Sun
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Mengyun
M
Wang
BGI-Shenzhen, Shenzhen, 518083, China.
Dan
D
Li
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Rui
R
Wang
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Science, Shanghai, 200031, China.
Fuming
F
Li
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Science, Shanghai, 200031, China.
Rong
R
Fang
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Yunjian
Y
Pan
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Xiaoyang
X
Luo
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Jing
J
He
BGI-Shenzhen, Shenzhen, 518083, China.
Liangtao
L
Zheng
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Science, Shanghai, 200031, China.
Jufeng
J
Xia
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Lixin
L
Qiu
BGI-Shenzhen, Shenzhen, 518083, China.
Jun
J
He
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Ting
T
Ye
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Ruoxin
R
Zhang
BGI-Shenzhen, Shenzhen, 518083, China.
Minghui
M
He
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Meiling
M
Zhu
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Haichuan
H
Hu
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Tingyan
T
Shi
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Xiaoyan
X
Zhou
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Menghong
M
Sun
BGI-Shenzhen, Shenzhen, 518083, China.
Shilin
S
Tian
BGI-Shenzhen, Shenzhen, 518083, China.
Yong
Y
Zhou
BGI-Shenzhen, Shenzhen, 518083, China.
Qiaoxiu
Q
Wang
BGI-Shenzhen, Shenzhen, 518083, China.
Longyun
L
Chen
BGI-Shenzhen, Shenzhen, 518083, China.
Guangliang
G
Yin
BGI-Shenzhen, Shenzhen, 518083, China.
Jingya
J
Lu
BGI-Shenzhen, Shenzhen, 518083, China.
Renhua
R
Wu
BGI-Shenzhen, Shenzhen, 518083, China.
Guangwu
G
Guo
BGI-Shenzhen, Shenzhen, 518083, China.
Yingrui
Y
Li
BGI-Shenzhen, Shenzhen, 518083, China.
Xueda
X
Hu
BGI-Shenzhen, Shenzhen, 518083, China.
Lin
L
Li
BGI-Shenzhen, Shenzhen, 518083, China.
Asan
BGI-Shenzhen, Shenzhen, 518083, China.
Qin
Q
Wang
BGI-Shenzhen, Shenzhen, 518083, China.
Ye
Y
Yin
BGI-Shenzhen, Shenzhen, 518083, China.
Qiang
Q
Feng
BGI-Shenzhen, Shenzhen, 518083, China.
Bin
B
Wang
BGI-Shenzhen, Shenzhen, 518083, China.
Hang
H
Wang
BGI-Shenzhen, Shenzhen, 518083, China.
Mingbang
M
Wang
BGI-Shanghai, Eastern CHINA, BGI-Shenzhen, Shanghai, 201100, China.
Xiaonan
X
Yang
BGI-Shenzhen, Shenzhen, 518083, China.
Xiuqing
X
Zhang
BGI-Shenzhen, Shenzhen, 518083, China.
Huanming
H
Yang
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.
Li
L
Jin
Lab of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry and Jonsson Cancer Center, UCLA, Los Angeles, California, 90095, USA.
Cun-Yu
CY
Wang
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Science, Shanghai, 200031, China.
Hongbin
H
Ji
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Haiquan
H
Chen
BGI-Shenzhen, Shenzhen, 518083, China.|The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200, Denmark.|Department of Biology, University of Copenhagen, Copenhagen, 2200, Denmark.
Jun
J
Wang
Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Duke Cancer Institute, Duke University Medical Center, and Department of Medicine, Duke University School of Medicine, Durham, North Carolina, 27710, USA.
Qingyi
Q
Wei
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D002448:Cell Adhesion / Q000235:genetics*; D002681:China; D059472:Exome; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D009154:Mutation; D017421:Sequence Analysis