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; Odenthal, Margarete (2017). Evolution analysis of heterogeneous non-small cell lung carcinoma by ultra-deep sequencing of the mitochondrial genome. Scientific Reports, 7(1), p. 11069. Nature Publishing Group 10.1038/s41598-017-11345-3
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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 (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology |
UniBE Contributor: |
Vassella, Erik |
Subjects: |
500 Science > 570 Life sciences; biology |
ISSN: |
2045-2322 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Erik Vassella-Zürcher |
Date Deposited: |
16 Nov 2017 08:12 |
Last Modified: |
05 Dec 2022 15:08 |
Publisher DOI: |
10.1038/s41598-017-11345-3 |
PubMed ID: |
28894165 |
BORIS DOI: |
10.7892/boris.107109 |
URI: |
https://boris.unibe.ch/id/eprint/107109 |
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