The Pan-Tumor Landscape of Gene Amplifications and Copy Number Amplification Ratio for Established and…

Cohort studyClinical cancer research : an official journal of the American Association for Cancer Research· Jul 2026

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 … Alexa B Schrock

Molecular PathologyCohort studyQ1IF 9.3

ERBB2 AmpRatio predicts outcomes to HER2-directed therapy, agrees 90-95% with immunohistochemistry/FISH

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

Jessica K Lee … Alexa B Schrock

Clinical cancer research · Jul 2026

Background

Gene copy number (copy number) amplifications and protein overexpression are common drug targets, and detection relies on various methodologies, including next-generation sequencing-based copy number, immunohistochemistry (immunohistochemistry), and in situ hybridization (ISH).

Purpose

We investigated the pan-tumor landscape of amplifications and developed AmpRatio, a novel method of copy number quantitation.

Methods

Pan-tumor tissue (N = 486,340) and liquid (N = 85,635) samples underwent hybrid capture-based comprehensive genomic profiling.

n = 486,340

Results

in breast cancer, AmpRatio nearly matches immunohistochemistry/FISH HER2 calls

Gastroesophageal

90%

Breast

95%

More results

Amplifications 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%).

More results

Among patients treated with anti-HER2 therapies, ERBB2 AmpRatio significantly stratified outcomes within the ERBB2-amplified and immunohistochemistry-defined HER2+ and HER2-low/ultralow populations.

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Conclusion · 1 of 3

Copy number amplifications are prevalent and diverse biomarkers, and AmpRatio is variable across genes and tumor types.

Conclusion · 2 of 3

ERBB2 AmpRatio is associated with outcomes to HER2-directed therapies and may have utility alongside immunohistochemistry for clinical decision-making.

Conclusion · 3 of 3

With the increasing number of therapies targeting amplifications/overexpression, it will be important to define harmonized methods for copy number quantification for optimal patient selection.

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

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

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