Global metabolomic profiling of uterine leiomyomas

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http://hdl.handle.net/10138/303770

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Heinonen , H-R , Mehine , M , Mäkinen , N , Pasanen , A , Pitkänen , E , Karhu , A , Sarvilinna , N S , Sjöberg , J , Heikinheimo , O , Bützow , R , Aaltonen , L A & Kaasinen , E 2017 , ' Global metabolomic profiling of uterine leiomyomas ' , British Journal of Cancer , vol. 117 , no. 12 , pp. 1855-1864 . https://doi.org/10.1038/bjc.2017.361

Title: Global metabolomic profiling of uterine leiomyomas
Author: Heinonen, Hanna-Riikka; Mehine, Miika; Mäkinen, Netta; Pasanen, Annukka; Pitkänen, Esa; Karhu, Auli; Sarvilinna, Nanna S.; Sjöberg, Jari; Heikinheimo, Oskari; Bützow, Ralf; Aaltonen, Lauri A.; Kaasinen, Eevi
Contributor organization: Research Programs Unit
Department of Medical and Clinical Genetics
Genome-Scale Biology (GSB) Research Program
Department of Pathology
Lauri Antti Aaltonen / Principal Investigator
Department of Obstetrics and Gynecology
Genome Stability Group
HUS Gynecology and Obstetrics
HUSLAB
Medicum
Date: 2017-12-05
Language: eng
Number of pages: 10
Belongs to series: British Journal of Cancer
ISSN: 0007-0920
DOI: https://doi.org/10.1038/bjc.2017.361
URI: http://hdl.handle.net/10138/303770
Abstract: Background: Uterine leiomyomas can be classified into molecularly distinct subtypes according to their genetic triggers: MED12 mutations, HMGA2 upregulation, or inactivation of FH. The aim of this study was to identify metabolites and metabolic pathways that are dysregulated in different subtypes of leiomyomas. Methods: We performed global metabolomic profiling of 25 uterine leiomyomas and 17 corresponding myometrium specimens using liquid chromatography-tandem mass spectroscopy. Results: A total of 641 metabolites were detected. All leiomyomas displayed reduced homocarnosine and haeme metabolite levels. We identified a clearly distinct metabolomic profile for leiomyomas of the FH subtype, characterised by metabolic alterations in the tricarboxylic acid cycle and pentose phosphate pathways, and increased levels of multiple lipids and amino acids. Several metabolites were uniquely elevated in leiomyomas of the FH subtype, including N6-succinyladenosine and argininosuccinate, serving as potential biomarkers for FH deficiency. In contrast, leiomyomas of the MED12 subtype displayed reduced levels of vitamin A, multiple membrane lipids and amino acids, and dysregulation of vitamin C metabolism, a finding which was also compatible with gene expression data. Conclusions: The study reveals the metabolomic heterogeneity of leiomyomas and provides the requisite framework for strategies designed to target metabolic alterations promoting the growth of these prevalent tumours.
Subject: uterine leiomyomas
fibroids
metabolomics
MED12
FH
HMGA2
HLRCC
FUMARATE-HYDRATASE
VITAMIN-C
CANCER
MUTATIONS
FREQUENCY
TUMORS
TRANSFORMATION
INACTIVATION
3122 Cancers
Peer reviewed: Yes
Rights: cc_by_nc_sa
Usage restriction: openAccess
Self-archived version: publishedVersion


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