Estimating copy number using next-generation sequencing to determine ERBB2 amplification status

Kohei Nakamura, Eriko Aimono, Junna Oba, Hideyuki Hayashi, Shigeki Tanishima, Tetsu Hayashida, Tatsuyuki Chiyoda, Takeo Kosaka, Tomoyuki Hishida, Hirohumi Kawakubo, Minoru Kitago, Koji Okabayashi, Takeru Funakoshi, Hajime Okita, Sadakatsu Ikeda, Hiromasa Takaishi, Hiroshi Nishihara

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Assessing Erb-b2 receptor tyrosine kinase 2 (ERBB2) amplification status in breast and gastric cancer is necessary for deciding the best therapeutic strategy. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are currently used for assessing protein levels and gene copy number (CN), respectively. The use of next-generation sequencing (NGS) to measure ERBB2 CN in breast cancer is approved by the United States Federal Drug Administration as a companion diagnostic. However, a CN of less than 8 is evaluated as “equivocal”, which means that some ERBB2 amplification cases diagnosed as “HER2 negative” might be false-negative cases. We reviewed the results of gene profiling targeting 160 cancer-related genes in breast (N = 90) and non-breast (N = 19) cancer tissue, and compared the ERBB2 CN results with the IHC/FISH scores. We obtained an estimated CN from the measured CN by factoring in the histological proportion of tumor cells and found that an ERBB2-estimated CN of 3.2 or higher was concordant with the combined IHC/FISH outcome in 98.4% (88/90) of breast cancer cases, while this was not always evident among non-breast cancer cases. Therefore, NGS-estimated ERBB2 CN could be considered a diagnostic test for anti-HER2 therapy after the completion of adequate prospective clinical trials.

Original languageEnglish (US)
Article number36
JournalMedical Oncology
Volume38
Issue number4
DOIs
StatePublished - Apr 2021
Externally publishedYes

Keywords

  • Breast cancer
  • ERBB2
  • Gene copy number
  • Immunohistochemistry
  • Next-generation sequencing

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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