Proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients

Pathogenic mutations in fumarate hydratase ( FH ) drive hereditary leiomyomatosis and renal cell cancer (HLRCC) and increase the risk of developing uterine leiomyomas (ULMs). An integrated proteogenomic analysis of ULMs from HLRCC (n = 16; FH -mutation confirmed) and non-syndromic (NS) patients (n =...

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Published in:Scientific reports 2021-04, Vol.11 (1), p.9371-9371, Article 9371
Main Authors: Bateman, Nicholas W., Tarney, Christopher M., Abulez, Tamara, Soltis, Anthony R., Zhou, Ming, Conrads, Kelly, Litzi, Tracy, Oliver, Julie, Hood, Brian, Driggers, Paul, Viollet, Coralie, Dalgard, Clifton, Wilkerson, Matthew, Catherino, William, Hamilton, Chad A., Darcy, Kathleen M., Casablanca, Yovanni, Al-Hendy, Ayman, Segars, James, Conrads, Thomas P., Larry Maxwell, G.
Format: Article
Language:English
Subjects:
631/1647/2067
692/699/67/1517/1931
Antioxidants
Fibroids
Fumarase
Glycolysis
Humanities and Social Sciences
Inactivation
Kidney cancer
multidisciplinary
Mutation
Oxidative stress
Peptides
Science
Science (multidisciplinary)
Thioredoxin
Transcription
Tumor suppressor genes
Uterine cancer
Uterus
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Summary:Pathogenic mutations in fumarate hydratase ( FH ) drive hereditary leiomyomatosis and renal cell cancer (HLRCC) and increase the risk of developing uterine leiomyomas (ULMs). An integrated proteogenomic analysis of ULMs from HLRCC (n = 16; FH -mutation confirmed) and non-syndromic (NS) patients (n = 12) identified a significantly higher protein:transcript correlation in HLRCC (R = 0.35) vs. NS ULMs (R = 0.242, MWU p = 0.0015). Co-altered proteins and transcripts (228) included antioxidant response element (ARE) target genes, such as thioredoxin reductase 1 ( TXNRD1 ), and correlated with activation of NRF2-mediated oxidative stress response signaling in HLRCC ULMs. We confirm 185 transcripts previously described as altered between HLRCC and NS ULMs, 51 co-altered at the protein level and several elevated in HLRCC ULMs are involved in regulating cellular metabolism and glycolysis signaling. Furthermore, 367 S-(2-succino)cysteine peptides were identified in HLRCC ULMs, of which sixty were significantly elevated in HLRCC vs. NS ULMs (LogFC = 1.86, MWU p 
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-88585-x