Evidence map›Paper›PMID 41870274›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2026

The Pan-Tumor Landscape of Gene Amplifications and Copy Number Amplification Ratio for Established and Emerging Clinical Targets.

Jessica K Lee, Julia C F Quintanilha, Kuei-Ting Chen, Bernard Fendler, Candice Francheska B Tambaoan, Ryon Graf, Nicole Odzer, Lajos Pusztai, Maryam Lustberg, Harshabad Singh and 11 more

Abstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
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

21 authors.

Jessica K LeeFoundation Medicine, Inc., Boston, Massachusetts.ORCID 0000-0002-4333-5092
Julia C F QuintanilhaFoundation Medicine, Inc., Boston, Massachusetts.ORCID 0000-0001-6908-4474
Kuei-Ting ChenFoundation Medicine, Inc., Boston, Massachusetts.ORCID 0009-0003-7558-2447
Bernard FendlerFoundation Medicine, Inc., Boston, Massachusetts.ORCID 0000-0001-7352-0689
Candice Francheska B TambaoanFoundation Medicine, Inc., Boston, Massachusetts.ORCID 0000-0001-7736-1902
Ryon GrafFoundation Medicine, Inc., Boston, Massachusetts.ORCID 0000-0002-8065-4148
Nicole OdzerYale University School of Medicine, New Haven, Connecticut.ORCID 0000-0002-0641-4189
Lajos PusztaiYale University School of Medicine, New Haven, Connecticut.ORCID 0000-0001-9632-6686
Maryam LustbergYale University School of Medicine, New Haven, Connecticut.ORCID 0000-0001-8559-5645
Harshabad SinghMassachusetts General Brigham Cancer Institute, Boston, Massachusetts.ORCID 0000-0001-6295-2013
Matthew StricklandMassachusetts General Brigham Cancer Institute, Boston, Massachusetts.ORCID 0000-0001-7845-0712
Tess A O'MearaDana-Farber Cancer Institute , Boston, Massachusetts.ORCID 0000-0002-4778-2842
Sara M TolaneyDana-Farber Cancer Institute , Boston, Massachusetts.ORCID 0000-0002-5940-8671
Timothy A YapThe University of Texas MD Anderson Cancer Center , Houston, Texas.ORCID 0000-0002-2154-3309
Jeffrey RossFoundation Medicine, Inc., Boston, Massachusetts.ORCID 0000-0001-8494-2596
Amaya Gasco HernandezFoundation Medicine, Inc., Boston, Massachusetts.ORCID 0000-0002-2838-9076
Brennan DeckerFoundation Medicine, Inc., Boston, Massachusetts.ORCID 0000-0003-4516-7421
Richard S P HuangFoundation Medicine, Inc., Boston, Massachusetts.
Samuel J KlempnerMassachusetts General Brigham Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-4062-0808
Ethan S SokolFoundation Medicine, Inc., Boston, Massachusetts.ORCID 0000-0002-5480-8473
Alexa B SchrockFoundation Medicine, Inc., Boston, Massachusetts.ORCID 0000-0003-0106-9096

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeGene copy number (CN) amplifications and protein overexpression are common drug targets, and detection relies on various methodologies, including next-generation sequencing-based CN, immunohistochemistry (IHC), and in situ hybridization (ISH). We investigated the pan-tumor landscape of amplifications and developed AmpRatio, a novel method of CN quantitation. EXPERIMENTAL

designPan-tumor tissue (N = 486,340) and liquid (N = 85,635) samples underwent hybrid capture-based comprehensive genomic profiling. A genome-wide CN model for each sample was generated to estimate the purity, ploidy, and segment-level CN. AmpRatio was calculated by dividing gene CN/sample ploidy. A US-based deidentified clinicogenomic database was utilized to assess the relationship between ERBB2 AmpRatio and HER2 IHC/FISH and outcomes on anti-HER2 therapies.

resultsAmplifications with varying degrees of gain were reported in 38.6% of pan-tumor tissue samples, most frequently MYC (5.6%), 11q13 (5.2%), ERBB2 (5.2%), and CCNE1 (3.2%). ERBB2 AmpRatio was associated with HER2 positivity by IHC/FISH in gastroesophageal [overall percent agreement (OPA) 90%] and breast (OPA 95%) cancers. Among patients treated with anti-HER2 therapies, ERBB2 AmpRatio significantly stratified outcomes within the ERBB2-amplified and IHC-defined HER2+ and HER2-low/ultralow populations. High concordance (sensitivity 88%) of amplification detection in liquid biopsy versus tissue was associated with higher AmpRatio and ctDNA tumor fraction ≥20%.

conclusionsCN amplifications are prevalent and diverse biomarkers, and AmpRatio is variable across genes and tumor types. ERBB2 AmpRatio is associated with outcomes to HER2-directed therapies and may have utility alongside IHC for clinical decision-making. With the increasing number of therapies targeting amplifications/overexpression, it will be important to define harmonized methods for CN quantification for optimal patient selection.

Indexed as

Biomarkers, TumorDNA Copy Number VariationsGene AmplificationGene DosageNeoplasmsErb-b2 Receptor Tyrosine KinasesFemaleHigh-Throughput Nucleotide SequencingHumansIn Situ Hybridization, FluorescenceBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine Kinases

Identifiers

PMID41870274
PMCPMC13320176

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Registered trials

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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.