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Eur J Cancer. 2015 Sep;51(13):1803-11. doi: 10.1016/j.ejca.2015.06.107. Epub 2015 Jul 8.

Spectrum of gene mutations detected by next generation exome sequencing in brain metastases of lung adenocarcinoma.

Author information

1
Department of Medicine I, Medical University of Vienna, Austria; Comprehensive Cancer Center, Central Nervous System Unit (CCC-CNS), Medical University of Vienna, Austria.
2
Institute of Neurology, Medical University of Vienna, Austria; Comprehensive Cancer Center, Central Nervous System Unit (CCC-CNS), Medical University of Vienna, Austria.
3
Core facilities, Medical University of Vienna, Vienna, Austria.
4
Center for Integrative Bioinformatics Vienna (CIBIV), University of Vienna and Medical University of Vienna and Oxford NIHR Biomedical Research Centre, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
5
Immunology Outpatient Clinic, Schwarzspanierstraße 15/1/9, A-1090 Vienna, Austria.
6
Core facilities, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center, Central Nervous System Unit (CCC-CNS), Medical University of Vienna, Austria. Electronic address: berthold.streubel@meduniwien.ac.at.
7
Department of Pathology, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center, Central Nervous System Unit (CCC-CNS), Medical University of Vienna, Austria.

Abstract

BACKGROUND:

Brain metastases (BM) are a life-threatening complication. We aimed to analyse gene mutations in lung adenocarcinoma BM.

METHODS:

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 ALK, ROS1, MET and FGFR1 gene status assessed by FISH were available from previous studies in the majority of patients.

RESULTS:

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 TP53, KRAS and CDKN2A, which were affected in 35/76 (46.1%), 29/76 (38.2%) and 17/76 (22.4%) samples, respectively. Other potentially druggable alterations included EGFR mutations (3/76, 3.9% of samples), PIK3CA mutation (2/76, 2.6%), BRAF mutation (1/76, 1.3%) and SMO mutation (1/76, 1.3%). Presence of KRAS mutations was associated with positive smoking history (p=0.015, Chi square test) and presence of EGFR mutation correlated with unfavourable overall survival time from BM diagnosis (p=0.019, log rank test).

CONCLUSIONS:

Deleterious gene mutations, some of them with potential therapeutic implications, are found in a high fraction of lung adenocarcinoma BM.

KEYWORDS:

Adenocarcinoma; BRAF mutation; Brain metastases; EGFR mutation; Lung cancer

PMID:
26164066
DOI:
10.1016/j.ejca.2015.06.107
[Indexed for MEDLINE]

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