Evolution analysis of heterogeneous non-small cell lung carcinoma by ultra-deep sequencing of the mitochondrial genome.

Autor: Amer W; Institute of Pathology, University Hospital of Cologne, Cologne, Germany., Toth C; Institute of Pathology, University Hospital of Cologne, Cologne, Germany., Vassella E; Institute of Pathology, University Hospital of Bern, Bern, Switzerland., Meinrath J; Institute of Pathology, University Hospital of Cologne, Cologne, Germany., Koitzsch U; Institute of Pathology, University Hospital of Cologne, Cologne, Germany., Arens A; Qiagen Inc, Hilden, Germany., Huang J; Institute of Pathology, University Hospital of Cologne, Cologne, Germany., Eischeid H; Institute of Pathology, University Hospital of Cologne, Cologne, Germany., Adam A; Institute of Pathology, University Hospital of Cologne, Cologne, Germany., Buettner R; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.; Center of Integrative Oncology, University Clinic of Cologne and Bonn, Cologne, Germany.; Lung Cancer Group Cologne, University Hospital of Cologne, Cologne, Germany.; Center of Molecular Medicine of Cologne, University of Cologne, Cologne, Germany., Scheel A; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.; Center of Integrative Oncology, University Clinic of Cologne and Bonn, Cologne, Germany.; Lung Cancer Group Cologne, University Hospital of Cologne, Cologne, Germany., Schaefer SC; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.; Center of Integrative Oncology, University Clinic of Cologne and Bonn, Cologne, Germany.; Lung Cancer Group Cologne, University Hospital of Cologne, Cologne, Germany., Odenthal M; Institute of Pathology, University Hospital of Cologne, Cologne, Germany. m.odenthal@uni-koeln.de.; Center of Integrative Oncology, University Clinic of Cologne and Bonn, Cologne, Germany. m.odenthal@uni-koeln.de.; Center of Molecular Medicine of Cologne, University of Cologne, Cologne, Germany. m.odenthal@uni-koeln.de.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2017 Sep 11; Vol. 7 (1), pp. 11069. Date of Electronic Publication: 2017 Sep 11.
DOI: 10.1038/s41598-017-11345-3
Abstrakt: Accurate assessment of tumour heterogeneity is an important issue that influences prognosis and therapeutic decision in molecular pathology. Due to the shortage of protective histones and a limited DNA repair capacity, the mitochondrial (mt)-genome undergoes high variability during tumour development. Therefore, screening of mt-genome represents a useful molecular tool for assessing precise cell lineages and tracking tumour history. Here, we describe a highly specific and robust multiplex PCR-based ultra-deep sequencing technology for analysis of the whole mt-genome (wmt-seq) on low quality-DNA from formalin-fixed paraffin-embedded tissues. As a proof of concept, we applied the wmt-seq technology to characterize the clonal relationship of non-small cell lung cancer (NSCLC) specimens with multiple lesions (N = 43) that show either different histological subtypes (group I) or pulmonary adenosquamous carcinoma as striking examples of a mixed-histology tumour (group II). The application of wmt-seq demonstrated that most samples bear common mt-mutations in each lesion of an individual patient, indicating a single cell progeny and clonal relationship. Hereby we show the monoclonal origin of histologically heterogeneous NSCLC and demonstrate the evolutionary relation of NSCLC cases carrying heteroplasmic mt-variants.
Databáze: MEDLINE