Show simple item record

dc.contributor.authorPenkert, Judith
dc.contributor.authorMärtens, Andre
dc.contributor.authorSeifert, Martin
dc.contributor.authorAuber, Bernd
dc.contributor.authorDerlin, Katja
dc.contributor.authorHille-Betz, Ursula
dc.contributor.authorHörmann, Philipp
dc.contributor.authorKlopp, Norman
dc.contributor.authorProkein, Jana
dc.contributor.authorSchlicker, Lisa
dc.contributor.authorWacker, Frank
dc.contributor.authorWallaschek, Hannah
dc.contributor.authorSchlegelberger, Brigitte
dc.contributor.authorHiller, Karsten
dc.contributor.authorRipperger, Tim
dc.contributor.authorIllig, Thomas
dc.date.accessioned2021-05-11T14:23:44Z
dc.date.available2021-05-11T14:23:44Z
dc.date.issued2021-04-07
dc.identifier.citationFront Oncol. 2021 Apr 7;11:627217. doi: 10.3389/fonc.2021.627217.en_US
dc.identifier.issn2234-943X
dc.identifier.pmid33898308
dc.identifier.doi10.3389/fonc.2021.627217
dc.identifier.urihttp://hdl.handle.net/10033/622866
dc.description.abstractIndividuals carrying a pathogenic germline variant in the breast cancer predisposition gene BRCA1 (gBRCA1+) are prone to developing breast cancer. Apart from its well-known role in DNA repair, BRCA1 has been shown to powerfully impact cellular metabolism. While, in general, metabolic reprogramming was named a hallmark of cancer, disrupted metabolism has also been suggested to drive cancer cell evolution and malignant transformation by critically altering microenvironmental tissue integrity. Systemic metabolic effects induced by germline variants in cancer predisposition genes have been demonstrated before. Whether or not systemic metabolic alterations exist in gBRCA1+ individuals independent of cancer incidence has not been investigated yet. We therefore profiled the plasma metabolome of 72 gBRCA1+ women and 72 age-matched female controls, none of whom (carriers and non-carriers) had a prior cancer diagnosis and all of whom were cancer-free during the follow-up period. We detected one single metabolite, pyruvate, and two metabolite ratios involving pyruvate, lactate, and a metabolite of yet unknown structure, significantly altered between the two cohorts. A machine learning signature of metabolite ratios was able to correctly distinguish between gBRCA1+ and controls in ~82%. The results of this study point to innate systemic metabolic differences in gBRCA1+ women independent of cancer incidence and raise the question as to whether or not constitutional alterations in energy metabolism may be involved in the etiology of BRCA1-associated breast cancer.en_US
dc.language.isoenen_US
dc.publisherFrontiersen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectBRCA1 germline mutationen_US
dc.subjectHIF1 alphaen_US
dc.subjectNAD+ balanceen_US
dc.subjectaerobic glycolysisen_US
dc.subjectbreast canceren_US
dc.subjectenergy metabolismen_US
dc.subjectlactateen_US
dc.subjectplasma metabolomeen_US
dc.titlePlasma Metabolome Signature Indicative of Germline Status Independent of Cancer Incidence.en_US
dc.typeArticleen_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalFrontiers in oncologyen_US
dc.source.volume11
dc.source.beginpage627217
dc.source.endpage
refterms.dateFOA2021-05-11T14:23:45Z
dc.source.journaltitleFrontiers in oncology
dc.source.countrySwitzerland


Files in this item

Thumbnail
Name:
Penkert et al.pdf
Size:
1.088Mb
Format:
PDF
Description:
Open Access publication

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International