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

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)

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:

25 Oct 2019 07:12

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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