RRC ID 62236
Author Liu J, McCleland M, Stawiski EW, Gnad F, Mayba O, Haverty PM, Durinck S, Chen YJ, Klijn C, Jhunjhunwala S, Lawrence M, Liu H, Wan Y, Chopra V, Yaylaoglu MB, Yuan W, Ha C, Gilbert HN, Reeder J, Pau G, Stinson J, Stern HM, Manning G, Wu TD, Neve RM, de Sauvage FJ, Modrusan Z, Seshagiri S, Firestein R, Zhang Z.
Title Integrated exome and transcriptome sequencing reveals ZAK isoform usage in gastric cancer.
Journal Nat Commun
Abstract Gastric cancer is the second leading cause of worldwide cancer mortality, yet the underlying genomic alterations remain poorly understood. Here we perform exome and transcriptome sequencing and SNP array assays to characterize 51 primary gastric tumours and 32 cell lines. Meta-analysis of exome data and previously published data sets reveals 24 significantly mutated genes in microsatellite stable (MSS) tumours and 16 in microsatellite instable (MSI) tumours. Over half the patients in our collection could potentially benefit from targeted therapies. We identify 55 splice site mutations accompanied by aberrant splicing products, in addition to mutation-independent differential isoform usage in tumours. ZAK kinase isoform TV1 is preferentially upregulated in gastric tumours and cell lines relative to normal samples. This pattern is also observed in colorectal, bladder and breast cancers. Overexpression of this particular isoform activates multiple cancer-related transcription factor reporters, while depletion of ZAK in gastric cell lines inhibits proliferation. These results reveal the spectrum of genomic and transcriptomic alterations in gastric cancer, and identify isoform-specific oncogenic properties of ZAK.
Volume 5
Pages 3830
Published 2014-5-8
DOI 10.1038/ncomms4830
PII ncomms4830
PMID 24807215
PMC PMC4024760
MeSH Base Sequence Cell Line Cell Proliferation / genetics Gene Expression Profiling High-Throughput Nucleotide Sequencing Humans MAP Kinase Kinase Kinases Microsatellite Instability Microsatellite Repeats / genetics Oligonucleotide Array Sequence Analysis Polymorphism, Single Nucleotide Protein Isoforms / genetics* Protein Kinases / genetics* Receptor, ErbB-2 / genetics Sequence Analysis, DNA Stomach Neoplasms / genetics* Transcriptome / genetics
IF 12.121
Human and Animal Cells KE-39(RCB1434) KE-97(RCB1435)