Next-generation assessment of human growth factor receptor 2 (ERBB2) amplification status: Clinical validation in the context of a hybrid capture-based, comprehensive solid tumor genomic profiling assay Journal Article


Authors: Ross, D. S.; Zehir, A.; Cheng, D. T.; Benayed, R.; Nafa, K.; Hechtman, J. F.; Janjigian, Y. Y.; Weigelt, B.; Razavi, P.; Hyman, D. M.; Baselga, J.; Berger, M. F.; Ladanyi, M.; Arcila, M. E.
Article Title: Next-generation assessment of human growth factor receptor 2 (ERBB2) amplification status: Clinical validation in the context of a hybrid capture-based, comprehensive solid tumor genomic profiling assay
Abstract: Establishing ERBB2 [human epidermal growth factor receptor 2 (HER2)] amplification status in breast and gastric carcinomas is essential to treatment selection. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) constitute the current standard for assessment. With further advancements in genomic medicine, new clinically relevant biomarkers are rapidly emerging and options for targeted therapy are increasing in patients with advanced disease, driving the need for comprehensive molecular profiling. Next-generation sequencing (NGS) is an attractive approach for up-front comprehensive assessment, including ERBB2 status, but the concordance with traditional methods of HER2 assessment is not well established. The Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay, a hybrid capture-based NGS assay interrogating the coding regions of 410 cancer-related genes, was performed on manually macrodissected unstained sections from formalin-fixed, paraffin-embedded breast (n = 213) and gastroesophageal (n = 39) tumors submitted for clinical mutation profiling. ERBB2 status was assessed using a custom bioinformatics pipeline, and NGS results were compared to IHC and FISH. NGS ERBB2 amplification calls had an overall concordance of 98.4% (248/252) with the combined IHC/FISH results in this validation set. Discrepancies occurred in the context of low tumor content and HER2 heterogeneity. ERBB2 amplification status can be reliably determined by hybridization capture-based NGS methods, allowing efficient concurrent testing for other potentially actionable genomic alterations, particularly in limited material. © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology
Journal Title: Journal of Molecular Diagnostics
Volume: 19
Issue: 2
ISSN: 1525-1578
Publisher: Elsevier Science, Inc.  
Date Published: 2017-03-01
Start Page: 244
End Page: 254
Language: English
DOI: 10.1016/j.jmoldx.2016.09.010
PROVIDER: scopus
PUBMED: 28027945
PMCID: PMC5397722
DOI/URL:
Notes: Article -- Export Date: 2 March 2017 -- Source: Scopus
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MSK Authors
  1. Khedoudja Nafa
    181 Nafa
  2. Yelena Yuriy Janjigian
    145 Janjigian
  3. Marc Ladanyi
    863 Ladanyi
  4. David Hyman
    181 Hyman
  5. Ahmet Zehir
    149 Zehir
  6. Michael Forman Berger
    380 Berger
  7. Maria Eugenia Arcila
    336 Arcila
  8. Dara Stacy Ross
    42 Ross
  9. Britta Weigelt
    260 Weigelt
  10. Donavan Tai Suan Cheng
    51 Cheng
  11. Jose T Baselga
    395 Baselga
  12. Pedram Razavi
    24 Razavi
  13. Rym Benayed
    68 Benayed