RT Journal
A1 Liu, Jinfeng
A1 Lee, William
A1 Jiang, Zhaoshi
A1 Chen, Zhongqiang
A1 Jhunjhunwala, Suchit
A1 Haverty, Peter M.
A1 Gnad, Florian
A1 Guan, Yinghui
A1 Gilbert, Houston N.
A1 Stinson, Jeremy
A1 Klijn, Christiaan
A1 Guillory, Joseph
A1 Bhatt, Deepali
A1 Vartanian, Steffan
A1 Walter, Kimberly
A1 Chan, Jocelyn
A1 Holcomb, Thomas
A1 Dijkgraaf, Peter
A1 Johnson, Stephanie
A1 Koeman, Julie
A1 Minna, John D.
A1 Gazdar, Adi F.
A1 Stern, Howard M.
A1 Hoeflich, Klaus P.
A1 Wu, Thomas D.
A1 Settleman, Jeff
A1 de Sauvage, Frederic J.
A1 Gentleman, Robert C.
A1 Neve, Richard M.
A1 Stokoe, David
A1 Modrusan, Zora
A1 Seshagiri, Somasekar
A1 Shames, David S.
A1 Zhang, Zemin
T1 Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events
JF Genome Research 
JO Genome Research 
YR 2012 
FD December 01 
VO 22 
IS 12 
SP 2315 
OP 2327 
DO 10.1101/gr.140988.112 
UL http://genome.cshlp.org/content/22/12/2315.abstract 
AB Lung cancer is a highly heterogeneous disease in terms of both underlying genetic lesions and response to therapeutic treatments. We performed deep whole-genome sequencing and transcriptome sequencing on 19 lung cancer cell lines and three lung tumor/normal pairs. Overall, our data show that cell line models exhibit similar mutation spectra to human tumor samples. Smoker and never-smoker cancer samples exhibit distinguishable patterns of mutations. A number of epigenetic regulators, including KDM6A, ASH1L, SMARCA4, and ATAD2, are frequently altered by mutations or copy number changes. A systematic survey of splice-site mutations identified 106 splice site mutations associated with cancer specific aberrant splicing, including mutations in several known cancer-related genes. RAC1b, an isoform of the RAC1 GTPase that includes one additional exon, was found to be preferentially up-regulated in lung cancer. We further show that its expression is significantly associated with sensitivity to a MAP2K (MEK) inhibitor PD-0325901. Taken together, these data present a comprehensive genomic landscape of a large number of lung cancer samples and further demonstrate that cancer-specific alternative splicing is a widespread phenomenon that has potential utility as therapeutic biomarkers. The detailed characterizations of the lung cancer cell lines also provide genomic context to the vast amount of experimental data gathered for these lines over the decades, and represent highly valuable resources for cancer biology.