Abstract 4671: Dual mutational changes of ALK gene fusion combined with EGFR or K-ras oncogenes in lung adenocarcinomas

Purpose The mutations of the EGFR, K-ras or ALK oncogenes are closely associated with tumorigenesis and progression of lung adenocarcinoma. Their mutational changes are known to be mutually exclusive, but double oncogenic mutations of ALK combined with EGFR or K-ras gene are rarely found. We analyzed the clinical impacts of double oncogenic mutations on clinical characteristics and treatment outcome, according to EGFR, K-ras, ALK mutation or triple negative (EGFR, K-ras, ALK wild) in lung adenocarcinomas. Patients and Methods For one hundred ninety six lung cancer patients conformed histologically as adenocarcinoma, we examined activating EGFR (exons 18 and 21) and K-ras (exon 2 and 3) mutations by direct nucleotide sequencing and. ALK gene rearrangements by FISH using break-apart probe. Among 196 patients, 86 patients (43.9%) were triple negative adenocarcinoma, 73 patients (37.2%) presented with activating EGFR mutation, 17 patients (8.7%) with ALK and 13 patients (6.6%) with K-ras mutation. Median age of 17 patients harboring ALK rearrangement was 54 years (range 25∼79), approximately 7 years younger than the patient population harboring EGFR or K-ras mutation (62 and 61 years, respectively). Fifteen patients (88.2%) had stage III or IV and 9 patients (52.9%) were never smoker. Platinum doublet chemotherapy or EGFR TKIs was administered for 14 patients initially presented as stage IV disease or recurred as metastatic disease after local treatment. The median PFS of the patients receiving platinum doublet chemotherapy and EGFR TKIs as first-line treatment was 5.67 months (range 2.97-20.9) and 3.58 months (range 3.53-3.63), respectively. Of 17 ALK-positive patients, dual oncogenic mutations of ALK together with either EGFR or K-ras were identified in 7 patients (3.6%). Six patients (85.7%) receiving platinum-doublet or EGFR TKI as initial treatment. showed partial response, and 1 patient (14.3%) showed stable disease. These seven patients are all alive at present. Conclusion Taken together, our data suggest the existence of dual oncogenic mutations in lung adenocarcinomas is not infrequent. We are undergoing the experiment for detection for circulating tumor cells harboring ALK rearrangements, EGFR or K-ras mutation in these patients' peripheral blood. Citation Format: Jieun Lee, Suk Hee Hong, Eun Kyung Jeon, Jung Oh Kim, Seung Joon Kim, Young Kyoon Kim, Jae Gil Park, Sook-Whan Sung, Tae-Jung Kim, Jin Hyoung Kang. Dual mutational changes of ALK gene fusio