Evidence map›Paper›PMID 25712460›Full record

ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2015

Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing.

C H Chung, V B Guthrie, D L Masica, C Tokheim, H Kang, J Richmon, N Agrawal, C Fakhry, H Quon, R M Subramaniam and 10 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed
20.7field-weighted citation impact, top 1% 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

110 citing papers in PubMed, 202 citations in OpenAlex.

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50 more citing papers are in PubMed but not listed here.

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

20 authors at 3 institutions in 1 country.

C H ChungDepartment of Oncology; Department of Otolaryngology-Head and Neck Surgery. Electronic address: cchung11@jhmi.edu.
V B GuthrieDepartment of Biomedical Engineering, Institute for Computational Medicine.
D L MasicaDepartment of Biomedical Engineering, Institute for Computational Medicine.
C TokheimDepartment of Biomedical Engineering, Institute for Computational Medicine.
H KangDepartment of Oncology.
J RichmonDepartment of Otolaryngology-Head and Neck Surgery.
N AgrawalDepartment of Otolaryngology-Head and Neck Surgery.
C FakhryDepartment of Oncology; Department of Otolaryngology-Head and Neck Surgery; Department of Milton J. Dance Head and Neck Center, Baltimore.
H QuonDepartment of Radiation Oncology.
R M SubramaniamDepartment of Oncology; Department of Otolaryngology-Head and Neck Surgery; Department of Radiology and Radiological Sciences.
Z ZuoDepartment of Medicine, University of Chicago, Chicago.
T SeiwertDepartment of Medicine, University of Chicago, Chicago.
Z R ChalmersFoundation Medicine, Inc., Cambridge, USA.
G M FramptonFoundation Medicine, Inc., Cambridge, USA.
S M AliFoundation Medicine, Inc., Cambridge, USA.
R YelenskyFoundation Medicine, Inc., Cambridge, USA.
P J StephensFoundation Medicine, Inc., Cambridge, USA.
V A MillerFoundation Medicine, Inc., Cambridge, USA.
R KarchinDepartment of Oncology; Department of Biomedical Engineering, Institute for Computational Medicine.
J A BishopDepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore.
Foundation Medicine (United States)University of Chicago · USJohns Hopkins Medicine · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
NCI NIH HHS P30 CA006973
6 · The paper itself

Abstract

backgroundTo determine genomic alterations in head and neck squamous cell carcinoma (HNSCC) using formalin-fixed, paraffin-embedded (FFPE) tumors obtained through routine clinical practice, selected cancer-related genes were evaluated and compared with alterations seen in frozen tumors obtained through research studies. PATIENTS AND

methodsDNA samples obtained from 252 FFPE HNSCC were analyzed using next-generation sequencing-based (NGS) clinical assay to determine sequence and copy number variations in 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer. Human papillomavirus (HPV) status was determined by presence of the HPV DNA sequence in all samples and corroborated with high-risk HPV in situ hybridization (ISH) and p16 immunohistochemical (IHC) staining in a subset of tumors. Sequencing data from 399 frozen tumors in The Cancer Genome Atlas and University of Chicago public datasets were analyzed for comparison.

resultsAmong 252 FFPE HNSCC, 84 (33%) were HPV positive and 168 (67%) were HPV negative by sequencing. A subset of 40 tumors with HPV ISH and p16 IHC results showed complete concordance with NGS-derived HPV status. The most common genes with genomic alterations were PIK3CA and PTEN in HPV-positive tumors and TP53 and CDKN2A/B in HPV-negative tumors. In the pathway analysis, the PI3K pathway in HPV-positive tumors and DNA repair-p53 and cell cycle pathways in HPV-negative tumors were frequently altered. The HPV-positive oropharynx and HPV-positive nasal cavity/paranasal sinus carcinoma shared similar mutational profiles.

conclusionThe genomic profile of FFPE HNSCC tumors obtained through routine clinical practice is comparable with frozen tumors studied in research setting, demonstrating the feasibility of comprehensive genomic profiling in a clinical setting. However, the clinical significance of these genomic alterations requires further investigation through application of these genomic profiles as integral biomarkers in clinical trials.

Indexed as

High-Throughput Nucleotide SequencingAdultAgedAged, 80 and overBiomarkers, TumorCarcinoma, Squamous CellCyclin-Dependent Kinase Inhibitor p16Databases, GeneticDNA Copy Number VariationsDNA, ViralFemaleFixativesFormaldehydeGene Expression ProfilingGenetic Association StudiesGenetic Predisposition to DiseaseBiomarkers, TumorCyclin-Dependent Kinase Inhibitor p16DNA, ViralFixativesFormaldehydecopy number variationDNA mutationhead and neck squamous cell carcinomahuman papillomavirus

Identifiers

PMID25712460
PMCPMC4516044
OpenAlexW2100405559

What OpenQuestion holds

Textmetadata
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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.