Germline variation networks in the PI3K/AKT pathway corresponding to familial high-incidence lung cancer pedigrees
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RESEARCH ARTICLE
Open Access
Germline variation networks in the PI3K/ AKT pathway corresponding to familial high-incidence lung cancer pedigrees Huan Lin1,2†, Gong Zhang3†, Xu-chao Zhang1†, Xin-lei Lian3, Wen-zhao Zhong1, Jian Su1, Shi-liang Chen1 and Yi-long Wu1*
Abstract Background: There were scarcely germline variants of familial lung cancer (LC) identified. We conducted an study with whole-exome sequencing of pedigrees with familial lung cancer to analyze the potential genetic susceptibility. Methods: Probands with the highest hereditary background were identified by our large-scale epidemiological study and five ones were enrolled as a learning set. The germline SNPs (single-nucleotide polymorphisms) of other five similar probands, four healthy individuals in the formerly pedigrees and three patients with sporadic LC were used as a validation set, controlled by three healthy individuals without family history of any cancer. The network of mutated genes was generated using STRING-DB and visualized using Cytoscape. Results: Specific and shared somatic mutations and germline SNPs were not the shared cause of familial lung cancer. However, individual germline SNPs showed distinct protein-protein interaction network patterns in probands versus healthy individuals and patients with sporadic lung cancer. SNP-containing genes were enriched in the PI3K/AKT pathway. These results were validated in the validation set. Furthermore, patients with familial lung cancer were distinguished by many germline variations in the PI3K/AKT pathway by a simple SVM classification method. It is worth emphasizing that one person with many germline variations in the PI3K/AKT pathway developed lung cancer during follow-up. Conclusions: The phenomenon that the enrichments of germline SNPs in the PI3K/AKT pathway might be a major predictor of familial susceptibility to lung cancer. Keywords: PI3K/AKT pathway, Familial lung cancer, Germline variation networks, Whole-exome sequencing
* Correspondence: [email protected] † Huan Lin, Gong Zhang, and Xu-chao Zhang should be regarded as joint First Authors. 1 Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, 106, Zhongshan Er Rd, Guangzhou 510080, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you
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