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

Autor:	Debeljak M; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Cho S; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Downs BM; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA., Considine M; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Avin-McKelvey B; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Wang Y; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Perez PN; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Grizzle WE; Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA., Hoadley KA; Department of Genetics, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Lynch CF; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA, USA., Hernandez BY; Population Sciences in the Pacific-Program, University of Hawaii Cancer Research Center, Honolulu, HI, USA., van Diest PJ; Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands., Cozen W; Department of Medicine, School of Medicine, Susan and Henry Samueli College of Health Sciences, University of California at Irvine, Irvine, CA, USA., Hamilton AS; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Hawes D; Department of Pathology and Laboratory Medicine, Keck School of Medicine, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA., Gabrielson E; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Cimino-Mathews A; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Florea LD; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Cope L; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Biostatistics, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Umbricht CB; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. cumbrich@jhmi.edu.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. cumbrich@jhmi.edu.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. cumbrich@jhmi.edu.; The Johns Hopkins University School of Medicine, Ross Building, Room 743, 720 Rutland Ave, Baltimore, MD, 21205, USA. cumbrich@jhmi.edu.
Jazyk:	angličtina
Zdroj:	Breast cancer research : BCR [Breast Cancer Res] 2024 Dec 04; Vol. 26 (1), pp. 178. Date of Electronic Publication: 2024 Dec 04.
DOI:	10.1186/s13058-024-01927-1
Abstrakt:	Background: Ductal 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. Methods: We 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. Results: We 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. Conclusion: DCIS 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. Competing Interests: Declarations. Ethics approval and consent to participate: All tissue samples were obtained from each institution’s archival tissue banks with respective institution’s Institutional Review Board approval. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. (© 2024. The Author(s).)
Databáze:	MEDLINE
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