Transcriptome and genome evolution during HER2-amplified breast neoplasia.
Background: The acquisition of oncogenic drivers is a critical feature of cancer progression. For some carcinomas, it is clear that certain genetic drivers occur early in neoplasia and others late. Why these drivers are selected and how these changes alter the neoplasia's fitness is less understood....
| Publicado en: | Breast Cancer Research Vol. 23; no. 1; pp. 1 - 16 |
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| Autores principales: | , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
BioMed Central
7/15/2021
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=151438324&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 151438324 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14655411 8UYJ jtl: Breast Cancer Research issn: 14655411 maglogo: N pubinfo: dt: 7/15/2021 vid: 23 iid: 1 pid: 24147 pub: BioMed Central artinfo: ui: 151438324 151438324 NLM34266469 151438324 10.1186/s13058-021-01451-6 NLM34266469 151438324 ppf: 1 ppct: 15 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Transcriptome and genome evolution during HER2-amplified breast neoplasia. aug: au: Lu, Peipei Foley, Joseph Zhu, Chunfang McNamara, Katherine Sirinukunwattana, Korsuk Vennam, Sujay Varma, Sushama Fehri, Hamid Srivastava, Arunima Zhu, Shirley Rittscher, Jens Mallick, Parag Curtis, Christina West, Robert affil: Department of Pathology, Stanford University, Stanford, CA, USA sug: subj: Breast Neoplasms Adenocarcinoma Gene Expression Profiling Genome, Human Receptors, Cell Surface Evolution Oncogenes Gene Amplification In Situ Hybridization, Fluorescence Genetics Signal Transduction Breast Neoplasms Pathology Adenocarcinoma Pathology Extracellular Space Interferons Metabolism Female Human Comparative Studies Multicenter Studies Evaluation Research Validation Studies Clinical Assessment Tools Female ab: Background: The acquisition of oncogenic drivers is a critical feature of cancer progression. For some carcinomas, it is clear that certain genetic drivers occur early in neoplasia and others late. Why these drivers are selected and how these changes alter the neoplasia's fitness is less understood.Methods: Here we use spatially oriented genomic approaches to identify transcriptomic and genetic changes at the single-duct level within precursor neoplasia associated with invasive breast cancer. We study HER2 amplification in ductal carcinoma in situ (DCIS) as an event that can be both quantified and spatially located via fluorescence in situ hybridization (FISH) and immunohistochemistry on fixed paraffin-embedded tissue.Results: By combining the HER2-FISH with the laser capture microdissection (LCM) Smart-3SEQ method, we found that HER2 amplification in DCIS alters the transcriptomic profiles and increases diversity of copy number variations (CNVs). Particularly, interferon signaling pathway is activated by HER2 amplification in DCIS, which may provide a prolonged interferon signaling activation in HER2-positive breast cancer. Multiple subclones of HER2-amplified DCIS with distinct CNV profiles are observed, suggesting that multiple events occurred for the acquisition of HER2 amplification. Notably, DCIS acquires key transcriptomic changes and CNV events prior to HER2 amplification, suggesting that pre-amplified DCIS may create a cellular state primed to gain HER2 amplification for growth advantage.Conclusion: By using genomic methods that are spatially oriented, this study identifies several features that appear to generate insights into neoplastic progression in precancer lesions at a single-duct level. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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