Evidence map›Paper›PMID 31830557›Full record

ArticleCancer letters2020

Somatic mitochondrial mutation discovery using ultra-deep sequencing of the mitochondrial genome reveals spatial tumor heterogeneity in head and neck squamous cell carcinoma.

Adrian D Schubert, Esther Channah Broner, Nishant Agrawal, Nyall London, Alexander Pearson, Anuj Gupta, Neha Wali, Tanguy Y Seiwert, Sarah Wheelan, Mark Lingen and 9 more

Open access · greenAbstract read
In one paragraph

Article in Cancer letters, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Pooled it
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  5. Salivary biomarkers: a promising approach for predicting immunotherapy response in head and neck cancers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 5 institutions in 2 countries.

Adrian D SchubertDepartment of Otolaryngology and Head & Neck Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Esther Channah BronerDepartment of Otolaryngology and Head & Neck Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Nishant AgrawalDepartment of Surgery, University of Chicago, Chicago, IL, USA.
Nyall LondonDepartment of Otolaryngology and Head & Neck Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Alexander PearsonDepartment of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Anuj GuptaThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Neha WaliDepartment of Otolaryngology and Head & Neck Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Tanguy Y SeiwertDepartment of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Sarah WheelanThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Mark LingenDepartment of Pathology, University of Chicago, Chicago, IL, USA.
Kay MacleodThe Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA.
Hailey AllenDepartment of Otolaryngology and Head & Neck Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Aditi ChatterjeeInstitute of Bioinformatics, International Technology Park, Bangalore, Karnataka, India.
Saloura VassilikiThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Daria GaykalovaDepartment of Otolaryngology and Head & Neck Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Mohammad O HoqueDepartment of Otolaryngology and Head & Neck Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
David SidranskyDepartment of Otolaryngology and Head & Neck Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Karthik SureshDivision of Pulmonary Critical Care Medicine, Johns Hopkins University School of Medicine. Baltimore, MD, USA.
Evgeny IzumchenkoDepartment of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA. Electronic address: izumchen@uchicago.edu.
Johns Hopkins University · USUniversity of Chicago · USInstitute of Bioinformatics · INNational Cancer Institute · USUniversity of Illinois Chicago · US

Funding

TUMOR SUPPRESOR GENE PROMOTER HYPERMETHYLATION FOR DETECTION OF HEAD AND NECKP50DE019032 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI WESTRA, WILLIAM H · 2007 to 2016
$27.1M
Functions of BNIP3 in lipid metabolism in the liver and in hepatocellular carcinomaR01CA200310 · NCI · UNIVERSITY OF CHICAGO · PI KAY F MACLEOD · 2016 to 2026
$3.6M
Molecular progression model for HNSCCR37DE012588 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI SIDRANSKY, DAVID · 2004 to 2012
$3.3M
Delineating chromatin-related gene expression signatures as a function of HNSCC progressionR01DE027809 · NIDCR · UNIVERSITY OF MARYLAND BALTIMORE · PI GAYKALOVA, DARIA A, IZUMCHENKO, EVGENY (EUGENE) G · 2019 to 2023
$2.6M
Metabolic regulation of Ca2+ entry and endothelial-mesenchymal transition in pulmonary arterial hypertensionR01HL151530 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI SURESH, KARTHIK · 2021 to 2025
$2.0M
PQ 5 Exploring whole mitochondrial genome of screen detected pre-neoplastic lung lesions by novel approachesR01CA208709 · NCI · JOHNS HOPKINS UNIVERSITY · PI HOQUE, MOHAMMAD OBAIDUL, SIDRANSKY, DAVID · 2016 to 2020
$1.9M
(PQ5) Consequences of imbalanced mitophagy and mitochondrial biogenesis in cancerR01CA216242 · NCI · UNIVERSITY OF CHICAGO · PI MACLEOD, KAY F · 2017 to 2021
$1.6M
ROS-induced endothelial dysfunction in pulmonary arterial hypertensionK08HL132055 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI SURESH, KARTHIK · 2017 to 2021
$828k
A reasoned approach to combination therapy development in head and neck cancerK08DE026500 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PEARSON, ALEXANDER THOMAS · 2016 to 2020
$800k
NCI NIH HHS R01 CA200310NCI NIH HHS R01 CA208709NCI NIH HHS R01 CA216242NHLBI NIH HHS K08 HL132055NHLBI NIH HHS R01 HL151530NIDCR NIH HHS K08 DE026500NIDCR NIH HHS P50 DE019032NIDCR NIH HHS R01 DE027809NIDCR NIH HHS R37 DE012588
6 · The paper itself

Abstract

Mutations in mitochondrial DNA (mtDNA) have been linked to risk, progression, and treatment response of head and neck squamous cell carcinoma (HNSCC). Due to their clonal nature and high copy number, mitochondrial mutations could serve as powerful molecular markers for detection of cancer cells in bodily fluids, surgical margins, biopsies and lymph node (LN) metastasis, especially at sites where tumor involvement is not histologically apparent. Despite a pressing need for high-throughput, cost-effective mtDNA mutation profiling system, current methods for library preparation are still imperfect for detection of low prevalence heteroplasmic mutations. To this end, we have designed an ultra-deep amplicon-based sequencing library preparation approach that covers the entire mitochondrial genome. We sequenced mtDNA in 28 HNSCCs, matched LNs, surgical margins and bodily fluids, and applied multiregional sequencing approach on 14 primary tumors. Our results demonstrate that this quick, sensitive and cost-efficient method allows obtaining a snapshot on the mitochondrial heterogeneity, and can be used for detection of low frequency tumor-associated mtDNA mutations in LNs, sputum and serum specimens. These findings provide the foundation for using mitochondrial sequencing for risk assessment, early detection, and tumor surveillance.

Indexed as

Genome, MitochondrialPoint MutationAdultAgedAged, 80 and overDatabases, GeneticDNA, MitochondrialFemaleGenetic HeterogeneityHead and Neck NeoplasmsHigh-Throughput Nucleotide SequencingHumansLymphatic MetastasisMaleMiddle AgedReproducibility of ResultsDNA, MitochondrialCancerHead and neck squamous cell carcinoma (HNSCC)Mitochondrial DNA (mtDNA)MutationsSequencing

Identifiers

PMID31830557
PMCPMC6980748
OpenAlexW2996719554

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.