Amer, Wafa, Toth, Csaba, Vassella, Erik, Meinrath, Jeannine, Koitzsch, Ulrike, Arens, Anne, Huang, Jia, Eischeid, Hannah, Adam, Alexander, Buettner, Reinhard, Scheel, Andreas, Schaefer, Stephan C. and Odenthal, Margarete (2017). Evolution analysis of heterogeneous non-small cell lung carcinoma by ultra-deep sequencing of the mitochondrial genome. Sci Rep, 7. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Amer, WafaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toth, CsabaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vassella, ErikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meinrath, JeannineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koitzsch, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arens, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huang, JiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eischeid, HannahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Adam, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheel, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaefer, Stephan C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Odenthal, MargareteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-217869
DOI: 10.1038/s41598-017-11345-3
Journal or Publication Title: Sci Rep
Volume: 7
Date: 2017
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2045-2322
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CANCER SYSTEMS BIOLOGY; DNA MUTATIONS; BREAST-CANCER; STEM-CELLS; PROGRESSION; DELETIONS; UNCOVERS; NETWORKS; REVEALS; BENIGNMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/21786

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