Genomic Landscape Survey Identifies SRSF1 as a Key Oncodriver in Small Cell Lung Cancer.

PLoS Genet 2016 Apr 19;12(4):e1005895. Epub 2016 Apr 19.

Medimmune, Gaithersburg, Maryland, United States of America.

Small cell lung cancer (SCLC) is an aggressive disease with poor survival. A few sequencing studies performed on limited number of samples have revealed potential disease-driving genes in SCLC, however, much still remains unknown, particularly in the Asian patient population. Here we conducted whole exome sequencing (WES) and transcriptomic sequencing of primary tumors from 99 Chinese SCLC patients. Dysregulation of tumor suppressor genes TP53 and RB1 was observed in 82% and 62% of SCLC patients, respectively, and more than half of the SCLC patients (62%) harbored TP53 and RB1 mutation and/or copy number loss. Additionally, Serine/Arginine Splicing Factor 1 (SRSF1) DNA copy number gain and mRNA over-expression was strongly associated with poor survival using both discovery and validation patient cohorts. Functional studies in vitro and in vivo demonstrate that SRSF1 is important for tumorigenicity of SCLC and may play a key role in DNA repair and chemo-sensitivity. These results strongly support SRSF1 as a prognostic biomarker in SCLC and provide a rationale for personalized therapy in SCLC.

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http://dx.doi.org/10.1371/journal.pgen.1005895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836692PMC
April 2016
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References

(Supplied by CrossRef)
Small cell lung cancer
T Sher et al.
Mayo Clin. Proc 2008
FBXW7 and NOTCH1 mutations in childhood T cell acute lymphoblastic leukaemia and T cell non-Hodgkin lymphoma
MJ Park et al.
Br J Haematol 2009
The role of NOTCH1 signaling in T-ALL
A Adolfo et al.
Hematology Am Soc Hematol Educ Program 2009

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