Cancer‐related gene mutations and intratumoral genetic heterogeneity in human epidermal growth factor receptor 2 heterogeneous gastric cancer

Human epidermal growth factor receptor 2 (HER2) protein overexpression is associated with HER2 gene amplification, a critical driver oncogenetic change in gastric cancer. HER2 heterogeneity in advanced gastric cancer is associated with a poor prognosis and affects the clinical efficacy of trastuzuma...

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Published inPathology international Vol. 70; no. 11; pp. 865 - 870
Main Authors Kanayama, Kazuki, Imai, Hiroshi, Usugi, Eri, Matsuda, Chise, Ichishi, Masako, Hirokawa, Yoshifumi S., Watanabe, Masatoshi
Format Journal Article
LanguageEnglish
Published Tokyo Wiley Subscription Services, Inc 01.11.2020
Subjects
Cancer
cancer‐related gene
Epidermal growth factor
ErbB-2 protein
Gastric cancer
Gene amplification
Genes
Growth factors
Heterogeneity
human epidermal growth factor receptor 2 heterogeneity
intratumoral genetic heterogeneity
Molecular modelling
Monoclonal antibodies
Mutation
p53 Protein
Receptors
subclonal mutation
Targeted cancer therapy
Trastuzumab
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Summary:Human epidermal growth factor receptor 2 (HER2) protein overexpression is associated with HER2 gene amplification, a critical driver oncogenetic change in gastric cancer. HER2 heterogeneity in advanced gastric cancer is associated with a poor prognosis and affects the clinical efficacy of trastuzumab. However, the mechanisms of HER2 heterogeneity are not fully understood. Here, we examined whether HER2 heterogeneous gastric cancer exhibited intratumoral genetic heterogeneity in other cancer‐related genes. Two cases of advanced gastric cancer with HER2 heterogeneity were selected, and samples of HER2‐positive and HER2‐negative areas in each case were analyzed using a cancer‐associated multiple gene panel. In both cases, TP53 mutations were observed in both HER2‐positive and HER2‐negative areas, whereas many of the potential driver and passenger mutations differed between HER2‐positive and HER2‐negative areas. Overall, our findings demonstrated that HER2 heterogeneous gastric cancer exhibited intratumoral genetic heterogeneity in other cancer‐related genes and that the molecular mechanisms could differ between HER2‐positive and ‐negative areas.
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ISSN:1320-5463
1440-1827
DOI:10.1111/pin.13004