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Contrasting DCIS an...
Contrasting DCIS and invasive breast cancer by subtype suggests basal-like DCIS as distinct lesions
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- Bergholtz, Helga (author)
- Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, Oslo, Norway; Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway
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- Lien, Tonje G. (author)
- Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, Oslo, Norway
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- Swanson, David M. (author)
- Oslo Univ Hosp, Oslo Ctr Biostat & Epidemiol, Oslo, Norway
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- Frigessi, Arnoldo (author)
- Oslo Univ Hosp, Oslo Ctr Biostat & Epidemiol, Oslo, Norway; Univ Oslo, Dept Biostat, Oslo, Norway
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- Daidone, Maria Grazia (author)
- Fdn IRCCS Ist Nazl Tumori, Dept Appl Res & Tech Dev, Milan, Italy
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- Tost, Jörg (author)
- CEA Inst Biol Francois Jacob, Ctr Natl Rech Genom Humaine, Lab Epigenet & Environm, Evry, France
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- Wärnberg, Fredrik (author)
- Uppsala universitet,Endokrinkirurgi,Uppsala Acad Hosp, Dept Surg, Uppsala, Sweden
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- Sørlie, Therese (author)
- Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, Oslo, Norway; Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway
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(creator_code:org_t)
- 2020-06-17
- 2020
- English.
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In: npj Breast Cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 6:1
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Abstract
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- Ductal carcinoma in situ (DCIS) is a non-invasive type of breast cancer with highly variable potential of becoming invasive and affecting mortality. Currently, many patients with DCIS are overtreated due to the lack of specific biomarkers that distinguish low risk lesions from those with a higher risk of progression. In this study, we analyzed 57 pure DCIS and 313 invasive breast cancers (IBC) from different patients. Three levels of genomic data were obtained; gene expression, DNA methylation, and DNA copy number. We performed subtype stratified analyses and identified key differences between DCIS and IBC that suggest subtype specific progression. Prominent differences were found in tumors of the basal-like subtype: Basal-like DCIS were less proliferative and showed a higher degree of differentiation than basal-like IBC. Also, core basal tumors (characterized by high correlation to the basal-like centroid) were not identified amongst DCIS as opposed to IBC. At the copy number level, basal-like DCIS exhibited fewer copy number aberrations compared with basal-like IBC. An intriguing finding through analysis of the methylome was hypermethylation of multiple protocadherin genes in basal-like IBC compared with basal-like DCIS and normal tissue, possibly caused by long range epigenetic silencing. This points to silencing of cell adhesion-related genes specifically in IBC of the basal-like subtype. Our work confirms that subtype stratification is essential when studying progression from DCIS to IBC, and we provide evidence that basal-like DCIS show less aggressive characteristics and question the assumption that basal-like DCIS is a direct precursor of basal-like invasive breast cancer.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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