Transcriptome and genome evolution during HER2-amplified breast neoplasia

Autor: Sujay Vennam, Sushama Varma, Parag Mallick, Christina Curtis, Peipei Lu, Shirley Zhu, Chunfang Zhu, Joseph W. Foley, Jens Rittscher, Robert B. West, Katherine McNamara, Hamid Fehri, Arunima Srivastava, Korsuk Sirinukunwattana
Jazyk: angličtina
Rok vydání: 2022
Předmět:
0301 basic medicine
Genome evolution
DNA Copy Number Variations
Receptor
ErbB-2
Breast Neoplasms
Biology
Breast neoplasia
Transcriptome
Evolution
Molecular
03 medical and health sciences
0302 clinical medicine
Breast cancer
medicine
Humans
Copy-number variation
skin and connective tissue diseases
neoplasms
In Situ Hybridization
Fluorescence
RC254-282
Laser capture microdissection
medicine.diagnostic_test
Genome
Human
Oncogene Genomic evolution
Gene Amplification
Cancer
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Oncogenes
Ductal carcinoma
medicine.disease
Extracellular Matrix
030104 developmental biology
Carcinoma
Intraductal
Noninfiltrating
030220 oncology & carcinogenesis
ERBB2/HER2
Cancer research
Female
Interferons
Fluorescence in situ hybridization
Signal Transduction
Research Article
Zdroj: Breast Cancer Research, Vol 23, Iss 1, Pp 1-15 (2021)
Breast Cancer Research : BCR
Popis: 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.
Databáze: OpenAIRE
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