TY - JOUR
T1 - Prevalence of somatic mitochondrial mutations and spatial distribution of mitochondria in non-small cell lung cancer
AU - Kazdal, Daniel
AU - Harms, Alexander
AU - Endris, Volker
AU - Penzel, Roland
AU - Kriegsmann, Mark
AU - Eichhorn, Florian
AU - Muley, Thomas
AU - Stenzinger, Albrecht
AU - Pfarr, Nicole
AU - Weichert, Wilko
AU - Warth, Arne
N1 - Publisher Copyright:
© 2017 Cancer Research UK. All rights reserved.
PY - 2017/7/11
Y1 - 2017/7/11
N2 - Background:Mitochondria are considered relevant players in many tumour entities and first data indicate beneficial effects of mitochondria-targeted antioxidants in both cancer prevention and anticancer therapies. To further dissect the potential roles of mitochondria in NSCLC we comprehensively analysed somatic mitochondrial mutations, determined the spatial distribution of mitochondrial DNA within complete tumour sections and investigated the mitochondrial load in a large-scale approach.Methods:Whole mitochondrial genome sequencing of 26 matched tumour and non-neoplastic tissue samples extended by reviewing published data of 326 cases. Systematical stepwise real-time PCR quantification of mitochondrial DNA covering 16 whole surgical tumour sections. Immunohistochemical determination of the mitochondrial load in 171 adenocarcinoma and 145 squamous cell carcinoma.Results:Our results demonstrate very low recurrences (max. 1.7%) and a broad distribution of 456 different somatic mitochondrial mutations. Large inter- and intra-tumour heterogeneity were seen for mitochondrial DNA copy numbers in conjunction with a correlation to the predominant histological growth pattern. Furthermore, tumour cells had significantly higher mitochondrial level compared to adjacent stroma, whereas differences between tumour entities were negligible.Conclusions:Non-evident somatic mitochondrial mutations and highly varying mitochondrial DNA level delineate challenges for the approach of mitochondria-targeted anticancer therapies in NSCLC.
AB - Background:Mitochondria are considered relevant players in many tumour entities and first data indicate beneficial effects of mitochondria-targeted antioxidants in both cancer prevention and anticancer therapies. To further dissect the potential roles of mitochondria in NSCLC we comprehensively analysed somatic mitochondrial mutations, determined the spatial distribution of mitochondrial DNA within complete tumour sections and investigated the mitochondrial load in a large-scale approach.Methods:Whole mitochondrial genome sequencing of 26 matched tumour and non-neoplastic tissue samples extended by reviewing published data of 326 cases. Systematical stepwise real-time PCR quantification of mitochondrial DNA covering 16 whole surgical tumour sections. Immunohistochemical determination of the mitochondrial load in 171 adenocarcinoma and 145 squamous cell carcinoma.Results:Our results demonstrate very low recurrences (max. 1.7%) and a broad distribution of 456 different somatic mitochondrial mutations. Large inter- and intra-tumour heterogeneity were seen for mitochondrial DNA copy numbers in conjunction with a correlation to the predominant histological growth pattern. Furthermore, tumour cells had significantly higher mitochondrial level compared to adjacent stroma, whereas differences between tumour entities were negligible.Conclusions:Non-evident somatic mitochondrial mutations and highly varying mitochondrial DNA level delineate challenges for the approach of mitochondria-targeted anticancer therapies in NSCLC.
KW - NSCLC
KW - heterogeneity
KW - mtDNA copy number variations
KW - somatic mtDNA mutations
KW - spatial distribution
UR - http://www.scopus.com/inward/record.url?scp=85027065489&partnerID=8YFLogxK
U2 - 10.1038/bjc.2017.155
DO - 10.1038/bjc.2017.155
M3 - Article
C2 - 28557978
AN - SCOPUS:85027065489
SN - 0007-0920
VL - 117
SP - 220
EP - 226
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 2
ER -