Incidence of EGFR, KRAS, BRAF, ALK, and p53 alterations in a cohort of 161 consecutively tested patients from a certified lung cancer center, correlation with clinical characteristics and treatment outcome

Introduction: The aim of the study was to systematically analyze EGFR, KRAS, BRAF, ALK and p53 within the same cohort of patients, to correlate alterations with clinical characteristics and to potentially identify new prognostic/predictive markers. Methods: 161 patients from a single center diagnosed with lung cancer were studied for the presence of EGFR mutations, ALK rearrangements, KRAS codon 12/13/61 and BRAF V600E and G469A, as well as inactivating p53 mutations. Methods for the detection of EGFR mutations included Sanger Sequencing and hybridization based COBAS testing. ALK rearrangements were either tested by RT-PCR or ALK-FISH (break apart probe, Vysis). BRAF mutations were detected by allele specific PCR, KRAS and p53 by Sanger Sequencing. Clinical characteristics including smoking status was available in all patients.

Results: 161 consecutive patients at the lung cancer center of the Pius-Hospital Oldenburg were studied. The EGFR mutation rate was 22% (35/161) in all patients, 41% (26/63) in never-light smokers and 9% (7/78) in current/ex-smokers. ALK rearrangements were found in 3.7 (5/134) patients. KRAS mutations were, as EGFR mutations dependent on smoking status: mutation rate was 20% (29/143) in all patients, 6%(4/142) in never-light smokers and 28% (22/71) in ex- current smokers. P53 mutation rate was 48% (22/46), and not dependent on smoking status. P53 mutations in EGFR mt + patients were associated with inferior survival than p53WT. BRAF mutations were seldom (2/142). Conclusion: EGFR and ALK mutations were overrepresented in never-light smokers, BRAF and KRAS mutations were underrepresented. P53 mutations occurred independently of smoking status in combination with EGFR mutations, but not ALK- translocations. OS and PFS data will be presented at the meeting.