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The Human Tumor Atlas Network (HTAN) Breast Precancer Atlas: A Multi-Omic Integrative Analysis of Ductal Carcinoma in situ With Clinical Outcomes

72 Pages Posted: 25 Jun 2021 Publication Status: Review Complete

See all articles by Siri H. Strand

Siri H. Strand

Stanford University School of Medicine - Department of Pathology

Belén Rivero-Gutiérrez

Stanford University School of Medicine - Department of Pathology

Kathleen E. Houlahan

Stanford University School of Medicine - Stanford Cancer Institute

Jose A. Seoane

Stanford University School of Medicine - Stanford Cancer Institute

Lorraine King

Duke University - Department of Surgery

Tyler Risom

Stanford University - Department of Pathology

Lunden A. Simpson

Duke University - Department of Surgery

Sujay Vennam

Stanford University - Department of Pathology

Aziz Khan

Stanford University - Stanford Cancer Institute

Luis Cisneros

Arizona State University - School of Life Sciences

Timothy Hardman

Duke University - Department of Surgery

Bryan Harmon

Montefiore Medical Center - Department of Pathology

Fergus Couch

Mayo Clinic - Department of Pathology

Kristalyn Gallagher

University of North Carolina (UNC) at Chapel Hill - Department of Surgery

Mark Kilgore

University of Washington - Department of Pathology

Gabrielle B. Rocque

University of Alabama at Birmingham - Department of Hematology and Oncology

Angela DeMichele

University of Pennsylvania - Department of Medicine

Tari King

Dana-Farber Cancer Institute - Department of Surgery

Priscilla McAuliffe

University of Pittsburgh -Department of Surgery

Julie Nangia

Baylor College of Medicine - Department of Medicine

Joanna Lee

MD Anderson Cancer Center - Department of Surgery

Jennifer Tseng

University of Chicago - Department of Surgery

Ana Maria Storniolo

Indiana University - School of Medicine

Alastair Thompson

Baylor College of Medicine - Department of Surgery

Gaorav Gupta

University of North Carolina at Chapel Hill - Department of Radiation and Oncology

Robyn Burns

The EMMES Corporation - TBCRC

Deborah J. Veis

Washington University School of Medicine - Departments of Medicine and Pathology & Immunology

Katherine DeSchryver

Washington University School of Medicine - Departments of Pathology & Immunology

Chunfang Zhu

Stanford University School of Medicine - Department of Pathology

Magdalena Matusiak

Stanford University School of Medicine - Department of Pathology

Jason Wang

Stanford University School of Medicine - Department of Pathology

Shirley X. Zhu

Stanford University School of Medicine - Department of Pathology

Jen Tappenden

Washington University - Department of Surgery

Daisy Yi Ding

Stanford University - Department of Biomedical Data Science

Dadong Zhang

Duke University School of Medicine - Duke Cancer Institute

Jingqin Luo

Washington University - Department of Surgery

Shu Jiang

Washington University - Department of Surgery

Sushama Varma

Stanford University School of Medicine - Department of Pathology

Lauren Anderson

Duke University School of Medicine - Department of Surgery

Cody Straub

Duke University School of Medicine - Department of Surgery

Sucheta Srivastava

Stanford University School of Medicine - Department of Pathology

Christina Curtis

Stanford University School of Medicine - Stanford Cancer Institute

Rob Tibshirani

Stanford University - Department of Biomedical Data Science

Robert Michael Angelo

Stanford University School of Medicine - Department of Pathology

Allison Hall

Duke University School of Medicine - Department of Pathology

Kouros Owzar

Duke University School of Medicine - Department of Biostatistics & Bioinformatics

Kornelia Polyak

Dana-Farber Cancer Institute - Department of Medical Oncology

Carlo Maley

Arizona State University - School of Life Sciences

Jeffrey R. Marks

Duke University School of Medicine - Department of Surgery

Graham A. Colditz

Washington University - Department of Surgery; Washington University in St. Louis - Division of Public Health Sciences

E. Shelley Hwang

Duke University School of Medicine - Department of Surgery

Robert B. West

Stanford University School of Medicine - Department of Pathology

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Abstract

Ductal carcinoma in situ (DCIS) is the most commonly diagnosed precursor of invasive breast cancer (IBC), with variable propensity for progression. We have performed the first multiscale, integrated profiling of DCIS with clinical outcomes to identify predictors of subsequent ipsilateral breast events. We analyzed 677 DCIS samples from 481 patients with 7.1 years median follow-up from two independent cohorts. We made observations on DNA, RNA, and protein expression, and generated a de novo clustering scheme for DCIS that represents the fundamental transcriptomic organization at this early stage of breast neoplasia. Distinct DCIS stromal expression patterns and immune cell compositions were identified. We also found RNA expression patterns that correlate with later events in both cohorts. Our multiscale approach employed in situ methods to generate a spatially resolved atlas of breast precancers, where complementary modalities can be directly compared and correlated with conventional pathology findings, disease states, and clinical outcome.

Keywords: Ductal carcinoma in situ, RNA gene expression profiling, whole genome sequencing, multiplex immunohistochemistry, invasive breast cancer, precancer, outcome, human tumor atlas network, breast, tumor microenvironment

Suggested Citation

Strand, Siri H. and Rivero-Gutiérrez, Belén and Houlahan, Kathleen E. and Seoane, Jose A. and King, Lorraine and Risom, Tyler and Simpson, Lunden A. and Vennam, Sujay and Khan, Aziz and Cisneros, Luis and Hardman, Timothy and Harmon, Bryan and Couch, Fergus and Gallagher, Kristalyn and Kilgore, Mark and Rocque, Gabrielle B. and DeMichele, Angela and King, Tari and McAuliffe, Priscilla and Nangia, Julie and Lee, Joanna and Tseng, Jennifer and Storniolo, Ana Maria and Thompson, Alastair and Gupta, Gaorav and Burns, Robyn and Veis, Deborah J. and DeSchryver, Katherine and Zhu, Chunfang and Matusiak, Magdalena and Wang, Jason and Zhu, Shirley X. and Tappenden, Jen and Ding, Daisy Yi and Zhang, Dadong and Luo, Jingqin and Jiang, Shu and Varma, Sushama and Anderson, Lauren and Straub, Cody and Srivastava, Sucheta and Curtis, Christina and Tibshirani, Rob and Angelo, Robert Michael and Hall, Allison and Owzar, Kouros and Polyak, Kornelia and Maley, Carlo and Marks, Jeffrey R. and Colditz, Graham A. and Hwang, E. Shelley and West, Robert B., The Human Tumor Atlas Network (HTAN) Breast Precancer Atlas: A Multi-Omic Integrative Analysis of Ductal Carcinoma in situ With Clinical Outcomes. Available at SSRN: https://ssrn.com/abstract=3874170 or http://dx.doi.org/10.2139/ssrn.3874170
This version of the paper has not been formally peer reviewed.

Siri H. Strand

Stanford University School of Medicine - Department of Pathology ( email )

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

Belén Rivero-Gutiérrez

Stanford University School of Medicine - Department of Pathology ( email )

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

Kathleen E. Houlahan

Stanford University School of Medicine - Stanford Cancer Institute ( email )

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

Jose A. Seoane

Stanford University School of Medicine - Stanford Cancer Institute ( email )

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

Lorraine King

Duke University - Department of Surgery ( email )

Durham, NC 27715
United States

Tyler Risom

Stanford University - Department of Pathology ( email )

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

Lunden A. Simpson

Duke University - Department of Surgery ( email )

Durham, NC 27715
United States

Sujay Vennam

Stanford University - Department of Pathology ( email )

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

Aziz Khan

Stanford University - Stanford Cancer Institute ( email )

CA
United States

Luis Cisneros

Arizona State University - School of Life Sciences ( email )

Farmer Building 440G PO Box 872011
Tempe, AZ 85287
United States

Timothy Hardman

Duke University - Department of Surgery ( email )

Durham, NC 27715
United States

Bryan Harmon

Montefiore Medical Center - Department of Pathology

111 East 210th Street
Bronx, NY 10467
United States

Fergus Couch

Mayo Clinic - Department of Pathology ( email )

200 First Street SW
Rochester, MN (507) 284-2511 55905
United States

Kristalyn Gallagher

University of North Carolina (UNC) at Chapel Hill - Department of Surgery ( email )

4050 Burnett Womack Building
Chapel Hill, NC 27599
United States

Mark Kilgore

University of Washington - Department of Pathology

Seattle, WA 98195
United States

Gabrielle B. Rocque

University of Alabama at Birmingham - Department of Hematology and Oncology

Birmingham, AL 35294-4460
United States

Angela DeMichele

University of Pennsylvania - Department of Medicine

Philadelphia, PA 19104
United States

Tari King

Dana-Farber Cancer Institute - Department of Surgery

450 Brookline Avenue
Boston, MA 02215
United States

Priscilla McAuliffe

University of Pittsburgh -Department of Surgery

135 N Bellefield Ave
Pittsburgh, PA 15260
United States

Julie Nangia

Baylor College of Medicine - Department of Medicine

Joanna Lee

MD Anderson Cancer Center - Department of Surgery ( email )

1901 East Road, Unit 1950
Houston, TX 77030
United States

Jennifer Tseng

University of Chicago - Department of Surgery ( email )

United States

Ana Maria Storniolo

Indiana University - School of Medicine ( email )

340 W 10th St #6200
Indianapolis, IN 46202
United States

Alastair Thompson

Baylor College of Medicine - Department of Surgery

Gaorav Gupta

University of North Carolina at Chapel Hill - Department of Radiation and Oncology ( email )

102 Ridge Road
Chapel Hill, NC 27514
United States

Robyn Burns

The EMMES Corporation - TBCRC ( email )

401 N Washington St
# 700
Rockville, MD 20850
United States

Deborah J. Veis

Washington University School of Medicine - Departments of Medicine and Pathology & Immunology ( email )

One Brookings Drive
Campus Box 1208
Saint Louis, MO 63130-4899
United States

Katherine DeSchryver

Washington University School of Medicine - Departments of Pathology & Immunology ( email )

One Brookings Drive
Campus Box 1208
Saint Louis, MO 63130-4899
United States

Chunfang Zhu

Stanford University School of Medicine - Department of Pathology ( email )

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

Magdalena Matusiak

Stanford University School of Medicine - Department of Pathology ( email )

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

Jason Wang

Stanford University School of Medicine - Department of Pathology ( email )

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

Shirley X. Zhu

Stanford University School of Medicine - Department of Pathology ( email )

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

Jen Tappenden

Washington University - Department of Surgery ( email )

One Brookings Drive
Campus Box 1208
Saint Louis, MO MO 63130-4899
United States

Daisy Yi Ding

Stanford University - Department of Biomedical Data Science

Stanford, CA 94305
United States

Dadong Zhang

Duke University School of Medicine - Duke Cancer Institute

100 Fuqua Drive
Durham, NC 27708-0204
United States

Jingqin Luo

Washington University - Department of Surgery ( email )

One Brookings Drive
Campus Box 1208
Saint Louis, MO MO 63130-4899
United States

Shu Jiang

Washington University - Department of Surgery ( email )

One Brookings Drive
Campus Box 1208
Saint Louis, MO MO 63130-4899
United States

Sushama Varma

Stanford University School of Medicine - Department of Pathology ( email )

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

Lauren Anderson

Duke University School of Medicine - Department of Surgery ( email )

United States

Cody Straub

Duke University School of Medicine - Department of Surgery ( email )

Durham, NC 27715
United States

Sucheta Srivastava

Stanford University School of Medicine - Department of Pathology ( email )

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

Christina Curtis

Stanford University School of Medicine - Stanford Cancer Institute ( email )

CA
United States

Rob Tibshirani

Stanford University - Department of Biomedical Data Science

Robert Michael Angelo

Stanford University School of Medicine - Department of Pathology ( email )

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

Allison Hall

Duke University School of Medicine - Department of Pathology ( email )

Durham, NC
United States

Kouros Owzar

Duke University School of Medicine - Department of Biostatistics & Bioinformatics ( email )

United States

Kornelia Polyak

Dana-Farber Cancer Institute - Department of Medical Oncology

Carlo Maley

Arizona State University - School of Life Sciences ( email )

Farmer Building 440G PO Box 872011
Tempe, AZ 85287
United States

Jeffrey R. Marks

Duke University School of Medicine - Department of Surgery ( email )

100 Fuqua Drive
Durham, NC 27708-0204
United States

Graham A. Colditz

Washington University - Department of Surgery

One Brookings Drive
Campus Box 1208
Saint Louis, MO MO 63130-4899
United States

Washington University in St. Louis - Division of Public Health Sciences ( email )

660 S. Euclid Avenue
Campus Box 8100
St. Louis, MO 63110
United States
314-454-7940 (Phone)
314-454-7941 (Fax)

HOME PAGE: http://publichealthsciences.wustl.edu

E. Shelley Hwang

Duke University School of Medicine - Department of Surgery ( email )

Durham, NC 27715
United States

Robert B. West (Contact Author)

Stanford University School of Medicine - Department of Pathology ( email )

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

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