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

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.

Alterations of type II classical cadherin, cadherin‐10 (CDH10), is associated with pancreatic ductal adenocarcinomas

“…In addition, Biankin et al found aberrations in axon guidance pathway genes in pancreatic cancer genomes. Furthermore, mutations in CDH10 were identified in colorectal cancer and lung cancer recently . These findings are in line with our studies that variations in CDH10 coding or nearby genomic regions may play roles in pancreatic cancer.…”

“…Furthermore, mutations in CDH10 were identified in colorectal cancer and lung cancer recently. [20][21][22] These findings are in line with our studies that variations in CDH10 coding or nearby genomic regions may play roles in pancreatic cancer.…”

“…It is predominantly expressed in brain and is putatively involved in synaptic adhesions and in axon outgrowth and guidance . Recent studies further suggest that somatic mutations in CDH10 are associated with colorectal cancer, gastric cancer, and lung cancer . Therefore, it is of interest to clarify the association between genetic alterations in CDH10 and pancreatic cancer.…”

“…18,19 Recent studies further suggest that somatic mutations in CDH10 are associated with colorectal cancer, gastric cancer, and lung cancer. [20][21][22] Therefore, it is of interest to clarify the association between genetic alterations in CDH10 and pancreatic cancer.…”

Possible Risk Factors of Pulmonary Metastases in Patients With International Federation of Gynecology and Obstetrics Stage I Endometrioid-Type Endometrial Cancer

“…26,27 It has also been reported that, in lung squamous cancer cells, the knockdown of CDH10 promotes cell proliferation, soft agar colony formation, cell migration, and cell invasion, whereas the overexpression of CDH10 inhibits cell proliferation. 28 CDH10 was found to be frequently mutated in both lung squamous cell carcinoma and adenocarcinoma, which indicates the importance of CDH10 mutations in the development of nonYsmall cell lung cancer. 29 Taken together, we postulate that mutant CDH10 may play important roles, or at least partial roles, in the invasion and metastasis of EC.…”