DCIS genomic signatures define biology and correlate with clinical outcome: a Human Tumor Atlas Network (HTAN) analysis of TBCRC 038 and RAHBT cohorts
Siri H Strand,
Kathleen E. Houlahan,
Lunden A Simpson,
Priscilla F McAuliffe,
Anna Maria Storniolo,
Deborah J Veis,
Shirley X Zhu,
Daisy Yi Ding,
Robert Michael Angelo,
Jeffrey R. Marks,
Graham A Colditz,
E. Shelley Hwang,
Robert B West
Posted 16 Jun 2021
bioRxiv DOI: 10.1101/2021.06.16.448585
Posted 16 Jun 2021
Ductal carcinoma in situ (DCIS) is the most common precursor of invasive breast cancer (IBC), with variable propensity for progression. We have performed the first multiscale, integrated profiling of DCIS with clinical outcomes by analyzing 677 DCIS samples from 481 patients with 7.1 years median follow-up from the Translational Breast Cancer Research Consortium (TBCRC) 038 study and the Resource of Archival Breast Tissue (RAHBT) cohorts. We made observations on DNA, RNA, and protein expression, and generated a de novo clustering scheme for DCIS that represents a fundamental transcriptomic organization at this early stage of breast neoplasia. Distinct stromal expression patterns and immune cell compositions were identified. We found RNA expression patterns that correlate with later events. 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.
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