Whole-Exome Sequencing In Tumor Samples From Sequenom-Wild-Type, Alk Negative Stage Iv Lung Adenocarcinoma (Adc) Patients (P)

8070 Background: The majority of lung ADC tumors are characterized by specific genetic features with KRAS mutations (mut) seen in 20-30%, EGFR mut in 15%, EML4-ALK translocations in 5%, and ERBB2 mut in 2%, among others. Some of these genetic alterations are already being used for selecting targeted therapies. However, identification of additional genomic alterations is required. Methods: In the present ongoing study we perform whole-exome sequencing in paraffin-embedded tumor samples from OncoCarta v1.0 panel wild-type (no mut in hotspots of KRAS, EGFR, ERBB2, AKT1, BRAF, PIK3CA genes) and ALK negative (by FISH) stage IV ADC lung cancer p, and in their matched normal tissue samples. Results: To date, a total of 7 tumors and matched normal tissues have been successfully analyzed. We have detected mut in previously identified ADC genes, such as ERBB2, CTNNB1, TP53, SMAD4 or APC. Interestingly, mut were found in genes belonging to the proposed new cancer hallmark ‘epigenetic and RNA regulation’, such as BRD3, EPC1, PHF1 in almost every p included in our study. Regarding alterations that could be considered relevant for lung tumor pathogenesis/growth or as potential targets for treatment therapies, we were able to identify candidates in 4 of the 7 p. In one p, a case of a transmembrane domain ERBB2mut in exon 20 (p.E770delinsEAYVM) not previously detected by the OncoCarta v1.0 panel (that interrogates L755P, G776S/L/V/C, A775_G776insYVMA, P780_Y781insGSP, S779_P780insVGS mut) was found. In another p, three somatic mut in the BRCA1/2 genes were detected. Additionally, one p had an ALK point mut (p.P336K), for which no functional information is available, together with an APC mutation. In the remaining p, a non-hotspot mutation (although previously detected in a colorectal tumor) was found in CTNNB1. Conclusions: In this limited experience of whole-exome sequencing of a subgroup of stage IV lung ADC p, potentially targetable alterations not formerly detected by other techniques were found. We believe that genomic approaches to detecting alterations may be useful in clinical practice and will hopefully provide assistance in making treatment decisions.