Genomic Landscape of Non-Small Cell Lung Cancer in Smokers and Never-Smokers

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• 作者：Ramaswamy Govindan ; Li Ding ; Malachi Griffith ; Janakiraman Subramanian ; Nathan?D. Dees ; Krishna?L. Kanchi ; Christopher?A. Maher ; Robert Fulton ; Lucinda Fulton ; John Wallis ; Ken Chen ; Jason Walker ; S ; ra McDonald ; Ron Bose ; David Ornitz ; Donghai Xiong ; Ming You ; David?J. Dooling ; Mark Watson ; Elaine?R. Mardis ; et al.
• 刊名：Cell
• 出版年：2012
• 出版时间：14 September, 2012
• 年：2012
• 卷：150
• 期：6
• 页码：1121-1134
• 全文大小：13765 K

文摘

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Summary

We report the results of whole-genome and transcriptome sequencing of tumor and adjacent normal tissue samples from 17 patients with non-small cell lung carcinoma (NSCLC). We identified 3,726 point mutations and more than 90 indels in the coding sequence, with an average mutation frequency more than 10-fold higher in smokers than in never-smokers. Novel alterations in genes involved in chromatin modification and DNA repair pathways were identified, along with m>DACH1m>, m>CFTRm>, m>RELNm>, m>ABCB5m>, and m>HGFm>. Deep digital sequencing revealed diverse clonality patterns in both never-smokers and smokers. All validated m>EFGRm> and m>KRASm> mutations were present in the founder clones, suggesting possible roles in cancer initiation. Analysis revealed 14 fusions, including ROS1 and ALK, as well as novel metabolic enzymes. Cell-cycle and JAK-STAT pathways are significantly altered in lung cancer, along with perturbations in 54 genes that are potentially targetable with currently available drugs.