Evidence map›Paper›PMID 34266469›Full record

ArticleBreast cancer research : BCR2021

Transcriptome and genome evolution during HER2-amplified breast neoplasia.

Peipei Lu, Joseph Foley, Chunfang Zhu, Katherine McNamara, Korsuk Sirinukunwattana, Sujay Vennam, Sushama Varma, Hamid Fehri, Arunima Srivastava, Shirley Zhu and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Breast cancer research : BCR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.3field-weighted citation impact, top 51% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Laser capture microdissection.Nature reviews. Methods primers · 2025
    Article
  3. Review
  4. Article
  5. Novel insights from spatial transcriptome analysis in solid tumors.International journal of biological sciences · 2023
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 2 countries.

Peipei LuDepartment of Pathology, Stanford University, Stanford, CA, USA. peipeiluw@gmail.com.
Joseph FoleyDepartment of Pathology, Stanford University, Stanford, CA, USA.
Chunfang ZhuDepartment of Pathology, Stanford University, Stanford, CA, USA.
Katherine McNamaraDepartment of Medicine and Genetics, Stanford University, Stanford, CA, USA.
Korsuk SirinukunwattanaInstitute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK.
Sujay VennamDepartment of Pathology, Stanford University, Stanford, CA, USA.
Sushama VarmaDepartment of Pathology, Stanford University, Stanford, CA, USA.
Hamid FehriInstitute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK.
Arunima SrivastavaDepartment of Computer Science and Engineering, The Ohio State University, Columbus, OH, USA.
Shirley ZhuDepartment of Pathology, Stanford University, Stanford, CA, USA.
Jens RittscherInstitute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK.
Parag MallickDepartment of Radiology, Stanford University, Stanford, CA, USA.
Christina CurtisDepartment of Medicine and Genetics, Stanford University, Stanford, CA, USA.
Robert WestDepartment of Pathology, Stanford University, Stanford, CA, USA.
Stanford University · USUniversity of Oxford · GBThe Ohio State University · US

Funding

Genomic and Morphologic Predictor of High-Risk DCISR01CA193694 · NCI · STANFORD UNIVERSITY · PI WEST, ROBERT B · 2016 to 2020
$3.5M
Quantifying patient-specific tumor evolutionary dynamics and resistance mechanisms in HER2-positive breast cancers treated with targeted therapyF30CA239313 · NCI · STANFORD UNIVERSITY · PI MCNAMARA, KATHERINE LEE · 2019 to 2022
$136k
NCI NIH HHS F30 CA239313NCI NIH HHS R01 CA193694
6 · The paper itself

Abstract

backgroundThe 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.

methodsHere 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.

resultsBy 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.

conclusionBy 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.

Indexed as

Breast NeoplasmsCarcinoma, Intraductal, NoninfiltratingDNA Copy Number VariationsErb-b2 Receptor Tyrosine KinasesEvolution, MolecularExtracellular MatrixFemaleGene AmplificationGenome, HumanHumansIn Situ Hybridization, FluorescenceInterferonsOncogenesSignal TransductionTranscriptomeERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesInterferonsBreast neoplasiaERBB2/HER2Oncogene Genomic evolution

Identifiers

PMID34266469
PMCPMC8281634
OpenAlexW3113000453

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.