Lung Cancer: Lung Cancer IV |

Genomic Landscape Survey Identifies SRSF1 as a Key Oncodriver in Small Cell Lung Cancer FREE TO VIEW

Liyan Jiang, PhD; Hongbin Shen; Yihong Yao
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Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A328. doi:10.1016/j.chest.2016.02.341
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SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: To survey comprehensive genetic landscape of Chinese Small cell lung cancer (SCLC) patients with detailed clinical history to find key recurrent genetic alterations in DNA repair pathways which may influence chemotherapy outcomes in SCLC patients.

METHODS: Whole exome sequencing (WES) and transcriptomic sequencing of primary tumors from 99 Chinese SCLC patients was conducted, including 25 normal [normal adjacent tissue (NAT) or blood] and matched tumor pairs, and 74 tumors only (no normal tissue). Functional studies in vitro and in vivo were performed to comfirm the potential target discovered in WES.

RESULTS: The most frequent transition and transversion changes were G>A and G>T, respectively. Genes harboring the most recurrent somatic SNVs or indels were TP53 (81%), RB1 (46%), CSMD3 (43%), OBSCN (41%), and LRP1B (38%). Eighty-two percent (82%) of patients harbored ≥1 nonsilent somatic SNVs in a DNA repair gene besides TP53. SRSF1 was the only gene that correlated between both CN gain and mRNA over-expression as well as between over-expression and survival using a Cox proportion hazard (PH) regression model adjusting for age, gender, tumor stage, and chemotherapy status (p =0.034; HR=3.0). Patients with SRSF1 mRNA over-expression or CN gain demonstrated significantly worse survival. Subsequent functional studies invitro and invivo demonstrate that SRSF1 is essential for tumorigenecity of SCLC and plays a key role in DNA repair and chemo-sensitivity.

CONCLUSIONS:SRSF1 is a prognostic and therapeutic target in SCLC and provide a rationale for personalized therapy in SCLC.

CLINICAL IMPLICATIONS: SCLC is an aggressive disease with poor survival. Currently, Large-scale sequencing studies have revealed potential disease-driving genes in various cancers, however, much still remains unknown, particularly in the Asian patient population. In the present study, we found and identified that SRSF1 was a potential prognostic and therapeutic target in SCLC and provide a rationale for personalized therapy in SCLC.

DISCLOSURE: The following authors have nothing to disclose: Liyan Jiang, Hongbin Shen, Yihong Yao

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