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Genomic Landscape Survey Identifies SRSF1 as a Key Oncodriver in Small Cell Lung Cancer
Open accessAbstract
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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Comprehensive genomic characterization of squamous cell lung cancers
The Cancer Genome Atlas Research Network (2012) · Nature · doi:10.1038/nature11404 · Cited by 3,994
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Metadata
- Authors
- Jiang, L., Huang, J., Higgs, B. W., Hu, Z., Xiao, Z., Yao, X., Conley, S., Zhong, H., Liu, Z., Brohawn, P., Shen, D., Wu, S., Ge, X., Jiang, Y., Zhao, Y., Lou, Y., Morehouse, C., Zhu, W., Sebastian, Y., Czapiga, M., Oganesyan, V., Fu, H., Niu, Y., Zhang, W., Streicher, K., Tice, D., Zhao, H., Zhu, M., Xu, L., Herbst, R., Su, X., Gu, Y., Li, S., Huang, L., Gu, J., Han, B., Jallal, B., Shen, H., & Yao, Y.
- Venue
- PLOS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-04-19
- Volume
- 12
- Issue
- 4
- Pages
- e1005895
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- OpenAlex
- W2342358015
- Cited by
- 241
- References
- 4
- FWCI
- 6.18
- Type
- journal article
- Language
- en
- Open access
- gold
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- The paper
- Jiang, L., Huang, J., Higgs, B. W., Hu, Z., Xiao, Z., Yao, X., Conley, S., Zhong, H., Liu, Z., Brohawn, P., Shen, D., Wu, S., Ge, X., Jiang, Y., Zhao, Y., Lou, Y., Morehouse, C., Zhu, W., Sebastian, Y., . . . Yao, Y. (2016). Genomic Landscape Survey Identifies SRSF1 as a Key Oncodriver in Small Cell Lung Cancer. PLOS Genetics. https://doi.org/10.1371/journal.pgen.1005895
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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