PMID- 34266469
OWN - NLM
STAT- MEDLINE
DCOM- 20211231
LR  - 20211231
IS  - 1465-542X (Electronic)
IS  - 1465-5411 (Print)
IS  - 1465-5411 (Linking)
VI  - 23
IP  - 1
DP  - 2021 Jul 15
TI  - Transcriptome and genome evolution during HER2-amplified breast neoplasia.
PG  - 73
LID - 10.1186/s13058-021-01451-6 [doi]
LID - 73
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.
CI  - (c) 2021. The Author(s).
FAU - Lu, Peipei
AU  - Lu P
AD  - Department of Pathology, Stanford University, Stanford, CA, USA. 
      peipeiluw@gmail.com.
FAU - Foley, Joseph
AU  - Foley J
AD  - Department of Pathology, Stanford University, Stanford, CA, USA.
FAU - Zhu, Chunfang
AU  - Zhu C
AD  - Department of Pathology, Stanford University, Stanford, CA, USA.
FAU - McNamara, Katherine
AU  - McNamara K
AD  - Department of Medicine and Genetics, Stanford University, Stanford, CA, USA.
FAU - Sirinukunwattana, Korsuk
AU  - Sirinukunwattana K
AD  - Institute of Biomedical Engineering, Department of Engineering Science, 
      University of Oxford, Oxford, UK.
AD  - Big Data Institute/Li Ka Shing Centre for Health Information and Discovery, 
      University of Oxford, Oxford, UK.
FAU - Vennam, Sujay
AU  - Vennam S
AD  - Department of Pathology, Stanford University, Stanford, CA, USA.
FAU - Varma, Sushama
AU  - Varma S
AD  - Department of Pathology, Stanford University, Stanford, CA, USA.
FAU - Fehri, Hamid
AU  - Fehri H
AD  - Institute of Biomedical Engineering, Department of Engineering Science, 
      University of Oxford, Oxford, UK.
AD  - Big Data Institute/Li Ka Shing Centre for Health Information and Discovery, 
      University of Oxford, Oxford, UK.
FAU - Srivastava, Arunima
AU  - Srivastava A
AD  - Department of Computer Science and Engineering, The Ohio State University, 
      Columbus, OH, USA.
FAU - Zhu, Shirley
AU  - Zhu S
AD  - Department of Pathology, Stanford University, Stanford, CA, USA.
FAU - Rittscher, Jens
AU  - Rittscher J
AD  - Institute of Biomedical Engineering, Department of Engineering Science, 
      University of Oxford, Oxford, UK.
FAU - Mallick, Parag
AU  - Mallick P
AD  - Department of Radiology, Stanford University, Stanford, CA, USA.
FAU - Curtis, Christina
AU  - Curtis C
AD  - Department of Medicine and Genetics, Stanford University, Stanford, CA, USA.
FAU - West, Robert
AU  - West R
AD  - Department of Pathology, Stanford University, Stanford, CA, USA.
LA  - eng
GR  - F30 CA239313/CA/NCI NIH HHS/United States
GR  - R01 CA193694/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210715
PL  - England
TA  - Breast Cancer Res
JT  - Breast cancer research : BCR
JID - 100927353
RN  - 9008-11-1 (Interferons)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Breast Neoplasms/*genetics/pathology
MH  - Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology
MH  - DNA Copy Number Variations
MH  - Evolution, Molecular
MH  - Extracellular Matrix/genetics
MH  - Female
MH  - Gene Amplification
MH  - Genome, Human/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Interferons/metabolism
MH  - Oncogenes/genetics
MH  - Receptor, ErbB-2/*genetics
MH  - Signal Transduction/genetics
MH  - Transcriptome/*genetics
PMC - PMC8281634
OTO - NOTNLM
OT  - Breast neoplasia
OT  - ERBB2/HER2
OT  - Oncogene Genomic evolution
COIS- Not applicable. Competing interests The authors declare that they have no 
      competing interests.
EDAT- 2021/07/17 06:00
MHDA- 2022/01/01 06:00
PMCR- 2021/07/15
CRDT- 2021/07/16 05:37
PHST- 2020/12/03 00:00 [received]
PHST- 2021/07/03 00:00 [accepted]
PHST- 2021/07/16 05:37 [entrez]
PHST- 2021/07/17 06:00 [pubmed]
PHST- 2022/01/01 06:00 [medline]
PHST- 2021/07/15 00:00 [pmc-release]
AID - 10.1186/s13058-021-01451-6 [pii]
AID - 1451 [pii]
AID - 10.1186/s13058-021-01451-6 [doi]
PST - epublish
SO  - Breast Cancer Res. 2021 Jul 15;23(1):73. doi: 10.1186/s13058-021-01451-6.