Although chemotherapy and radiation therapy are effective against small cell lung cancer (SCLC), patients often only have a few months to live. Therapeutic choices are currently limited, and there are no clinically useful prognostic variables of responses to therapy. Researchers analyzed cBioPortal for information on 108 SCLCs, including clinical data and somatic mutations of genes included in the MSK-IMPACT panel. The data from 54 more SCLCs that were available in cBioPortal confirmed the first findings. Tumors of both short- and long-term survivors exhibited distinct network architectures. A gene’s degree (K) and betweenness (B) in its network of associated mutations were 2 defining characteristics. About 2 signatures of mutant genes, 1 for short (IL-7R, NTRK2, HNF-1A) and 1 for long survivors, were found by comparing their B/K ratio(NBN, PTPN-11, IRS-1, INPP-4A, PIK-3CG, HGF, LATS-2, SMARCA-4, FLT-3, EIF-4A2, SPEN, PAX-5, SH2-D1A, ARID-1A, HOXB-13, ERCC-4, FANCA, FH, FGFR-2, MST-1R, SMAD-4, DDR-2, IGF-1R, PIK-3CB). There was a statistically significant difference between the median overall survival times of patients with and without the short signature mutations (P<.001). There was a significant improvement in overall survival from 20 months to 39 months (P=.004) for patients with at least 1 altered gene in the extended signature. The brief signature’s utility was further validated in a new set of SCLCs from a different source. The gene mutation networks may be useful for subclassifying SCLCs according to the presence or absence of somatic mutations and for locating tumors with a poor prognosis.