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.