1463O - Prospective molecular evaluation of small cell lung cancer (SCLC) utilizing the comprehensive Mutation Analysis Program (MAP) at Memorial Sloan Ket...

Date 29 September 2014
Event ESMO 2014
Session SCLC and other thoracic malignancies
Topics Small Cell Lung Cancer
Pathology/Molecular Biology
Translational Research
Basic Scientific Principles
Basic Principles in the Management and Treatment (of cancer)
Presenter Lee Krug
Citation Annals of Oncology (2014) 25 (suppl_4): iv511-iv516. 10.1093/annonc/mdu355
Authors L.M. Krug1, M.C. Pietanza2, A.M. Varghese3, H. Won4, L. Wang4, N. Rekhtman4, W. Travis4, A. Litvak1, P.K. Paik1, G.J. Riely1, M.F. Zakowski4, M. Ladanyi4, M.F. Berger4, M. Kris1, C.M. Rudin1
  • 1Medicine/thoracic Oncology, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 2Medicine/thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 3Medicine/gastrointestinal Service, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 4Pathology, Memorial Sloan Kettering Cancer Center, 10065 - New York/US



Recent studies using next generation sequencing (NGS) on resected SCLC specimens have led to insights into the molecular heterogeneity of this disease. However, comprehensive, prospective molecular profiling of patients (pts) with advanced SCLC using the biopsy specimens available in clinical practice has not been performed.


Utilizing an IRB-approved protocol, we prospectively are evaluating SCLC tumors (SCLC-MAP) of pts in active treatment. These biopsies are evaluated by: fluorescence in situ hybridization (FISH) for FGFR1 and MET copy number; point mutation genotyping for known oncogenes by a mass spectrometry based assay (Sequenom); and NGS with a panel of 300 cancer-related genes. We first tested the feasibility of this approach in a series of pts with SCLC identified retrospectively, with matched tumor and normal pairs, and performed NGS, confirming the findings by FISH.


In the feasibility cohort, 21 pts with SCLC had FFPE samples available. After histologic review and DNA extraction, 10 pts had adequate material for NGS. We observed recurrent mutations in RB1 (N=7) and TP53 (N=8) and amplifications of FGFR1 (N=2) and MET (N=1), using as little as 15 nanograms of DNA. FISH confirmed FGFR1 and MET amplification in the identified cases. Since 2/2013, SCLC pts undergoing active treatment, with sufficient archived tissue, are providing consent for SCLC-MAP. Thus far, 36 pt samples have been tested. Sequenom (N=32) identified an AKT1 E17 mutation (N=1) and a PIK3CA E542K mutation (N=1). NGS (N=25) has yielded the following: loss of RB1 (N=18 mutations; N=4 deletions); mutations in TP53 (N=24), MLL3 (N=9), and EPHA 5 (N=9); and amplifications of CDKN2C (N=5), MYCL1 (N=3), SOX2 (N=2), and FGFR1 (N=1, confirmed by FISH). 4 pts had insufficient material.


Comprehensive molecular evaluation of SCLC is feasible on clinical specimens. Prospective collection of SCLC tumor samples and mutational analyses continue. Such analyses will allow us to characterize the molecular diversity of SCLC, identify pts who will be candidates for targeted therapies, and ascertain clinical characteristics. Funded, in part, by the Lung Cancer Research Foundation.


All authors have declared no conflicts of interest.