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Ali Maeve FitzGerald, Department of Biological Sciences, Munster Technological University, Bishopstown, Cork, Ireland 2 School of Science, Engineering and Food Science, University College Cork, Ireland 3Center of Functional Genomics, Berlin Institute of Health at Charité – Universitätsmedizin Berlin; Berlin, Germany 4Department of Hematology, Oncology and Cancer Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin; Berlin, GermanyFollow
Francesca Tiso, 3Center of Functional Genomics, Berlin Institute of Health at Charité – Universitätsmedizin Berlin; Berlin, Germany 4Department of Hematology, Oncology and Cancer Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin; Berlin, GermanyFollow
Kirsten Kübler, 3Center of Functional Genomics, Berlin Institute of Health at Charité – Universitätsmedizin Berlin; Berlin, Germany 4Department of Hematology, Oncology and Cancer Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin; Berlin, Germany 5German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany 6Cancer Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. 7Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School Teaching Hospital, Charlestown, Massachusetts, USA.Follow

Abstract

Ductal carcinoma in situ (DCIS) remains one of the most reported lesions detected by mammography screening programmes, yet our understanding of its progression to malignancy and markers of invasiveness is limited. Although a non-obligate precursor of invasive ductal carcinoma (IDC), all currently diagnosed DCIS patients are indiscriminately subjected to mastectomy or breast-conserving therapy (BCT) and radiotherapy. With less than 50% of untreated DCIS progressing to IDC, questions have been raised surrounding the over-treatment of indolent DCIS.

Thus, one of the central clinical challenges is to assess the risk of disease progression, which has prompted research efforts aimed at refining prognostic capabilities through a range of molecular techniques, including single-cell RNA sequencing (scRNA-seq). While providing valuable insights into the underlying tumour biology, a conclusive biomarker to detect patients most likely to progress from DCIS to invasiveness has yet to be identified.

This review reports genes that were highly expressed in DCIS based on 5 studies that performed scRNA-seq in 11 human DCIS samples and 2 murine models. Throughout the studies, the genes ERBB2, KRT18, EPCAM, and MYC consistently emerged as the most frequently proposed markers for DCIS. In addition, CPB1 and RPL17 have been hypothesised as potential future therapeutic targets, due to a decreased rate of DCIS cell growth witnessed when silenced.

Together, our combined data shows that while a few potential biomarkers have been proposed, there is substantial variation among the proposed molecular markers of DCIS. In future, additional scRNA-seq analysis of DCIS in larger cohort sizes is necessary to identify a conclusive marker capable of differentiating indolent from aggressive lesions.

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