Vis enkel innførsel

dc.contributor.authorFougner, Christianen_US
dc.contributor.authorBergholtz, Helgaen_US
dc.contributor.authorKuiper, Raoulen_US
dc.contributor.authorNorum, Jens Henriken_US
dc.contributor.authorSørlie, Thereseen_US
dc.PublishedFougner C, Bergholtz H, Kuiper R, Norum JH, Sørlie T. Claudin-low-like mouse mammary tumors show distinct transcriptomic patterns uncoupled from genomic drivers. Breast Cancer Research. 2019;21(85)eng
dc.description.abstractBackground Claudin-low breast cancer is a molecular subtype associated with poor prognosis and without targeted treatment options. The claudin-low subtype is defined by certain biological characteristics, some of which may be clinically actionable, such as high immunogenicity. In mice, the medroxyprogesterone acetate (MPA) and 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumor model yields a heterogeneous set of tumors, a subset of which display claudin-low features. Neither the genomic characteristics of MPA/DMBA-induced claudin-low tumors nor those of human claudin-low breast tumors have been thoroughly explored. Methods The transcriptomic characteristics and subtypes of MPA/DMBA-induced mouse mammary tumors were determined using gene expression microarrays. Somatic mutations and copy number aberrations in MPA/DMBA-induced tumors were identified from whole exome sequencing data. A publicly available dataset was queried to explore the genomic characteristics of human claudin-low breast cancer and to validate findings in the murine tumors. Results Half of MPA/DMBA-induced tumors showed a claudin-low-like subtype. All tumors carried mutations in known driver genes. While the specific genes carrying mutations varied between tumors, there was a consistent mutational signature with an overweight of T>A transversions in TG dinucleotides. Most tumors carried copy number aberrations with a potential oncogenic driver effect. Overall, several genomic events were observed recurrently; however, none accurately delineated claudin-low-like tumors. Human claudin-low breast cancers carried a distinct set of genomic characteristics, in particular a relatively low burden of mutations and copy number aberrations. The gene expression characteristics of claudin-low-like MPA/DMBA-induced tumors accurately reflected those of human claudin-low tumors, including epithelial-mesenchymal transition phenotype, high level of immune activation, and low degree of differentiation. There was an elevated expression of the immunosuppressive genes PTGS2 (encoding COX-2) and CD274 (encoding PD-L1) in human and murine claudin-low tumors. Conclusions Our findings show that the claudin-low breast cancer subtype is not demarcated by specific genomic aberrations, but carries potentially targetable characteristics warranting further research.en_US
dc.rightsAttribution CC BYeng
dc.subjectBreast cancereng
dc.subjectMouse modelseng
dc.titleClaudin-low-like mouse mammary tumors show distinct transcriptomic patterns uncoupled from genomic driversen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2019 The Author(s)
dc.source.journalBreast Cancer Research

Tilhørende fil(er)


Denne innførselen finnes i følgende samling(er)

Vis enkel innførsel

Attribution CC BY
Med mindre annet er angitt, så er denne innførselen lisensiert som Attribution CC BY