Significantly mutated genes and regulatory pathways in SCLC-a meta-analysis.

Varsha Sundaresan, Victor T Lin, Faming Liang, Frederic J Kaye, Reika Kawabata-Iwakawa, Kouya Shiraishi, Takashi Kohno, Jun Yokota, Lei Zhou

Journal: Cancer genetics 2017;216-217():20-28

PMID: 29025592

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Abstract

Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers and demands effective targeted therapeutic strategies. In this meta-analysis study, we aim to identify significantly mutated genes and regulatory pathways to help us better understand the progression of SCLC and to identify potential biomarkers. Besides ranking genes based on their mutation frequencies, we sought to identify statistically significant mutations in SCLC with the MutSigCV software. Our analysis identified several genes with relatively low mutation frequency, including PTEN, as highly significant (p < 0.001), suggesting these genes may play an important role in the progression of SCLC. Our results also indicated mutations in genes involved in the axon guidance pathways likely play an important role in SCLC progression. In addition, we observed that the mutation rate was significantly higher in samples with RB1 gene mutated when compared to samples with wild type RB1, suggesting that RB1 status has significant impact on the mutation profile and disease progression in SCLC.

Address: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA; UF Health Cancer Center, University of Florida, Gainesville, FL, USA.; Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA.; Department of Biostatistics, University of Florida, Gainesville, FL, USA.; UF Health Cancer Center, University of Florida, Gainesville, FL, USA; Department of Medicine, University of Florida, Gainesville, FL, USA; UF Genetics Institute, University of Florida, Gainesville, FL, USA.; Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.; Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Division of Translational Research, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Tokyo 104-0045, Japan.; Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Cancer Genome Biology Group, Institute of Predictive and Personalized Medicine of Cancer, Barcelona 08916, Spain.; Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA; UF Health Cancer Center, University of Florida, Gainesville, FL, USA; UF Genetics Institute, University of Florida, Gainesville, FL, USA. Electronic address: [email protected].

DOI: 10.1016/j.cancergen.2017.05.003

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MeSH Terms: Axon Guidance, Cluster Analysis, Databases, Genetic, Humans, Lung Neoplasms, Mutation, Mutation Rate, Retinoblastoma Protein, Signal Transduction, Small Cell Lung Carcinoma