Evidence map›Paper›PMID 39633428›Full record

ArticleBreast cancer research : BCR2024

Multimodal genome-wide survey of progressing and non-progressing breast ductal carcinoma in-situ.

Marija Debeljak, Soonweng Cho, Bradley M Downs, Michael Considine, Brittany Avin-McKelvey, Yongchun Wang, Phillip N Perez, William E Grizzle, Katherine A Hoadley, Charles F Lynch and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Breast cancer research : BCR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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

20 authors.

Marija DebeljakDepartment of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Soonweng ChoDepartment of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Bradley M DownsInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
Michael ConsidineDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Brittany Avin-McKelveyDepartment of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Yongchun WangDepartment of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Phillip N PerezDepartment of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
William E GrizzleDepartment of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA.
Katherine A HoadleyDepartment of Genetics, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Charles F LynchDepartment of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA, USA.
Brenda Y HernandezPopulation Sciences in the Pacific-Program, University of Hawaii Cancer Research Center, Honolulu, HI, USA.
Paul J van DiestDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Wendy CozenDepartment of Medicine, School of Medicine, Susan and Henry Samueli College of Health Sciences, University of California at Irvine, Irvine, CA, USA.
Ann S HamiltonDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Debra HawesDepartment of Pathology and Laboratory Medicine, Keck School of Medicine, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA.
Edward GabrielsonDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ashley Cimino-MathewsDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Liliana D FloreaDepartment of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Leslie CopeDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Christopher B UmbrichtDepartment of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. cumbrich@jhmi.edu.

Funding

UNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Stephanie Engel · 2001 to 2026
$36.3M
Multicenter Genetic, Epigenetic & Expression Analysis of DCIS outcome predictorsR01CA140311 · NCI · JOHNS HOPKINS UNIVERSITY · PI UMBRICHT, CHRISTOPHER B · 2011 to 2015
$2.6M
Discovery and validation of early molecular breast cancer risk markers in benign breast diseaseR01CA222779 · NCI · JOHNS HOPKINS UNIVERSITY · PI UMBRICHT, CHRISTOPHER B · 2018 to 2023
$2.3M
Computational Methods to Characterize Alternative Splicing from Massive Collections of RNA-seq DataR01GM129085 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI FLOREA, LILIANA D · 2019 to 2022
$1.5M
NCI NIH HHS R01 CA140311NCI NIH HHS R01CA140311NCI NIH HHS R01 CA222779NIEHS NIH HHS P30 ES010126NIGMS NIH HHS R01 GM129085
6 · The paper itself

Abstract

backgroundDuctal carcinoma in-situ (DCIS) is a pre-invasive form of invasive breast cancer (IBC). Due to improved breast cancer screening, it now accounts for ~ 25% of all breast cancers. While the treatment success rates are over 90%, this comes at the cost of considerable morbidity, considering that the majority of DCIS never become invasive and our understanding of the molecular changes occurring in DCIS that predispose to invasive disease is limited. The aim of this study is to characterize molecular changes that occur in DCIS, with the goal of improving DCIS risk stratification.

methodsWe identified and obtained a total of 197 breast tissue samples from 5 institutions (93 DCIS progressors, 93 DCIS non-progressors, and 11 adjacent normal breast tissues) that had at least 10-year follow-up. We isolated DNA and RNA from archival tissue blocks and characterized genome-wide mRNA expression, DNA methylation, DNA copy number variation, and RNA splicing variation.

resultsWe obtained all four genomic data sets in 122 of the 197 samples. Our intrinsic expression subtype-stratified analyses identified multiple molecular differences both between DCIS subtypes and between DCIS and IBC. While there was heterogeneity in molecular signatures and outcomes within intrinsic subtypes, several gene sets that differed significantly between progressing and non-progressing DCIS were identified by Gene Set Enrichment Analysis.

conclusionDCIS is a molecularly highly heterogenous disease with variable outcomes, and the molecular events determining DCIS disease progression remain poorly defined. Our genome-wide multi-omic survey documents DCIS-associated alterations and reveals molecular heterogeneity within the intrinsic DCIS subtypes. Further studies investigating intrinsic subtype-stratified characteristics and molecular signatures are needed to determine if these may be exploitable for risk assessment and mitigation of DCIS progression. The highly significant associations of specific gene sets with IBC progression revealed by our Gene Set Enrichment Analysis may lend themselves to the development of a prognostic molecular score, to be validated on independent DCIS cohorts.

Indexed as

Breast NeoplasmsCarcinoma, Intraductal, NoninfiltratingDisease ProgressionAdultAgedBiomarkers, TumorDNA Copy Number VariationsDNA MethylationFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenome-Wide Association StudyHumansMiddle AgedBiomarkers, TumorAlternative splicingDCIS progressionDNA copy number variationGene set enrichment analysisGenome-wide surveyMethylomeTranscriptome

Identifiers

PMID39633428
PMCPMC11616160

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Registered trials

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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.