ArticleGenome biology2015
Intra-tumor genetic heterogeneity and alternative driver genetic alterations in breast cancers with heterogeneous HER2 gene amplification.
Article in Genome biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 134 citations in OpenAlex.
- NSABP FB-10: a phase Ib/II trial evaluating ado-trastuzumab emtansine (T-DM1) with neratinib in women with metastatic HER2-positive breast cancer.Breast cancer research : BCR · 2024Trial
- HER2 status change in residual breast carcinoma after neoadjuvant HER2-targeted therapy in patients with HER2-positive breast cancer.Breast cancer research and treatment · 2026Article
- SECTOR: structural entropy-based learning of spatiotemporal organisation in spatial transcriptomics.Bioinformatics (Oxford, England) · 2026Article
- ERBB2 amplification is a late event in the pathogenesis of high-grade endometrial carcinomas with heterogeneous HER2 expression.The Journal of pathology · 2026Article
- HER2 Heterogeneity in Breast Cancer: Biological Basis, Clinical Implications, and Therapeutic Strategies.Breast cancer (Dove Medical Press) · 2026Review
- HER2 expression in breast cancer: evidence gaps and challenges.NPJ precision oncology · 2025Review
- Biallelic BRF2 mutations disrupt redox homeostasis as etiological factors in syndromic immunodeficiency and developmental disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Review
- Article
- Integrated single-cell analysis reveals distinct epigenetic-regulated cancer cell states and a heterogeneity-guided core signature in tamoxifen-resistant breast cancer.Genome medicine · 2024Article
- Spatial Biology of Breast Cancer.Cold Spring Harbor perspectives in medicine · 2024Review
- Impact of Resistance on Therapeutic Design: A Moran Model of Cancer Growth.Bulletin of mathematical biology · 2024Article
- Decreased HER2 expression in endometrial cancer following anti-HER2 therapy.The Journal of pathology · 2024Article
- In Vitro MRS of Cells Treated with Trastuzumab at 1.5 Tesla.International journal of molecular sciences · 2024Article
- Exploring Biomarkers in Breast Cancer: Hallmarks of Diagnosis, Treatment, and Follow-Up in Clinical Practice.Medicina (Kaunas, Lithuania) · 2024Review
- HER2 Genetic Intratumor Heterogeneity Is Associated With Resistance to Trastuzumab and Trastuzumab Emtansine Therapy in Recurrent High-Grade Endometrial Cancer.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2023Article
- HAHNet: a convolutional neural network for HER2 status classification of breast cancer.BMC bioinformatics · 2023Article
- Insights into the pleiotropic roles of ZNF703 in cancer.Heliyon · 2023Review
- Review
- Transcriptomic Changes Associated withCancers · 2022Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors at 8 institutions in 4 countries.
Funding
Abstract
backgroundHER2 is overexpressed and amplified in approximately 15% of invasive breast cancers, and is the molecular target and predictive marker of response to anti-HER2 agents. In a subset of these cases, heterogeneous distribution of HER2 gene amplification can be found, which creates clinically challenging scenarios. Currently, breast cancers with HER2 amplification/overexpression in just over 10% of cancer cells are considered HER2-positive for clinical purposes; however, it is unclear as to whether the HER2-negative components of such tumors would be driven by distinct genetic alterations. Here we sought to characterize the pathologic and genetic features of the HER2-positive and HER2-negative components of breast cancers with heterogeneous HER2 gene amplification and to define the repertoire of potential driver genetic alterations in the HER2-negative components of these cases.
resultsWe separately analyzed the HER2-negative and HER2-positive components of 12 HER2 heterogeneous breast cancers using gene copy number profiling and massively parallel sequencing, and identified potential driver genetic alterations restricted to the HER2-negative cells in each case. In vitro experiments provided functional evidence to suggest that BRF2 and DSN1 overexpression/amplification, and the HER2 I767M mutation may be alterations that compensate for the lack of HER2 amplification in the HER2-negative components of HER2 heterogeneous breast cancers.
conclusionsOur results indicate that even driver genetic alterations, such as HER2 gene amplification, can be heterogeneously distributed within a cancer, and that the HER2-negative components are likely driven by genetic alterations not present in the HER2-positive components, including BRF2 and DSN1 amplification and HER2 somatic mutations.
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