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

作者：Jessica Lee, Júlia C.F. Quintanilha, Kuei‐Ting Chen, Bernard Fendler, Candice Francheska B. Tambaoan, Ryon P. Graf, Nicole B. Odzer, Lajos Pusztai, Maryam B. Lustberg, Harshabad Singh, Matthew R. Strickland, Tess A. O’Meara, Sara M. Tolaney, Timothy A. Yap, Jeffrey S. Ross, Amaya Gascó Hernández, Brennan Decker, Richard S.P. Huang, Samuel J. Klempner, Ethan Sokol, Alexa B. Schrock · 年份：2026 · DOI：10.1158/1078-0432.c.8568744 · 研究领域：Cancer Genomics and Diagnostics、HER2/EGFR in Cancer Research、Microtubule and mitosis dynamics

<div>AbstractPurpose:Gene 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 Design:Pan-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.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%). 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...