TY  - JOUR
AU  - Penkert, Judith
AU  - Märtens, Andre
AU  - Seifert, Martin
AU  - Auber, Bernd
AU  - Derlin, Katja
AU  - Hille-Betz, Ursula
AU  - Hörmann, Philipp
AU  - Klopp, Norman
AU  - Prokein, Jana
AU  - Schlicker, Lisa
AU  - Wacker, Frank
AU  - Wallaschek, Hannah
AU  - Schlegelberger, Brigitte
AU  - Hiller, Karsten
AU  - Ripperger, Tim
AU  - Illig, Thomas
TI  - Plasma Metabolome Signature Indicative of BRCA1 Germline Status Independent of Cancer Incidence.
JO  - Frontiers in oncology
VL  - 11
SN  - 2234-943X
CY  - Lausanne
PB  - Frontiers Media
M1  - DKFZ-2021-00957
SP  - 627217
PY  - 2021
N1  - Division of Tumour Metabolism and Microenvironment, German Cancer Research Center (DKFZ), Heidelberg, Germany. 
AB  - Individuals 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
KW  - BRCA1 germline mutation (Other)
KW  - HIF1 alpha (Other)
KW  - NAD+ balance (Other)
KW  - aerobic glycolysis (Other)
KW  - breast cancer (Other)
KW  - energy metabolism (Other)
KW  - lactate (Other)
KW  - plasma metabolome (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:33898308
C2  - pmc:PMC8058469
DO  - DOI:10.3389/fonc.2021.627217
UR  - https://inrepo02.dkfz.de/record/168525
ER  -