Spectrum of gene mutations detected by next generation exome sequencing in brain metastases of lung adenocarcinoma. Issue 13 (September 2015)

• Record Type: Journal Article
• Authors: Preusser, Matthias; Berghoff, Anna S.; Koller, Romina; Zielinski, Christoph C.; Hainfellner, Johannes A.; Liebmann-Reindl, Sandra; Popitsch, Niko; Geier, Christoph B.; Streubel, Berthold; Birner, Peter
• Is Part Of: European journal of cancer. Volume 51:Issue 13(2015:Sep.)
• Page Start: 1803
• Page End: 1811
• Publication Date: 2015-09
• Subjects: Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2015.06.107
• Languages: English
• ISSNs: 0959-8049

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title id="st005">Abstract</title> <sec> <title id="st010">Background</title> <p id="sp0005">Brain metastases (BM) are a life-threatening complication. We aimed to analyse gene mutations in lung adenocarcinoma BM.</p> </sec> <sec> <title id="st015">Methods</title> <p id="sp0010">We performed next generation sequencing (NGS) of a pre-defined set of 48 cancer-related genes in a cohort of 76 neurosurgical lung adenocarcinoma BM specimens using a cancer specific gene panel on the MiSeq platform (Illumina, San Diego, CA). NGS results were statistically correlated to patient characteristics. Data on <italic>ALK</italic>, <italic>ROS1</italic>, <italic>MET</italic> and <italic>FGFR1</italic> gene status assessed by FISH were available from previous studies in the majority of patients.</p> </sec> <sec> <title id="st020">Results</title> <p id="sp0015">Twenty-nine (60.4%) of the 48 investigated cancer-related genes were mutated in at least one BM sample and 64 (84.2%) of the 76 BM samples carried at least one mutated gene. The number of mutated genes per sample ranged from 0 to 9 (median 2). The most commonly mutated genes were <italic>TP53</italic>, <italic>KRAS</italic> and <italic>CDKN2A</italic>, which were affected in 35/76 (46.1%), 29/76 (38.2%) and 17/76 (22.4%) samples, respectively. Other potentially druggable alterations included <italic>EGFR</italic> mutations (3/76, 3.9% of samples), <italic>PIK3CA</italic> mutation (2/76, 2.6%), <italic>BRAF</italic> mutation (1/76, 1.3%) and <italic>SMO</italic> mutation (1/76, 1.3%). Presence of <italic>KRAS</italic> mutations was associated with positive smoking history (<italic>p</italic> = 0.015, Chi square test) and presence of <italic>EGFR</italic> mutation correlated with unfavourable overall survival time from BM diagnosis (<italic>p</italic> = 0.019, log rank test).</p> </sec> <sec> <title id="st025">Conclusions</title> <p id="sp0020">Deleterious gene mutations, some of them with potential therapeutic implications, are found in a high fraction of lung adenocarcinoma BM.</p> </sec> </abstract>