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

Abstract 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) patient...

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Autores principales:	Nicholas W. Bateman, Christopher M. Tarney, Tamara Abulez, Anthony R. Soltis, Ming Zhou, Kelly Conrads, Tracy Litzi, Julie Oliver, Brian Hood, Paul Driggers, Coralie Viollet, Clifton Dalgard, Matthew Wilkerson, William Catherino, Chad A. Hamilton, Kathleen M. Darcy, Yovanni Casablanca, Ayman Al-Hendy, James Segars, Thomas P. Conrads, G. Larry Maxwell
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c023cf0dac914100a5bb9c69090f4b69
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spelling	oai:doaj.org-article:c023cf0dac914100a5bb9c69090f4b692021-12-02T17:39:22ZProteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients10.1038/s41598-021-88585-x2045-2322https://doaj.org/article/c023cf0dac914100a5bb9c69090f4b692021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88585-xhttps://doaj.org/toc/2045-2322Abstract 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 < 0.0001). These results confirm and define novel proteogenomic alterations in uterine leiomyoma tissues collected from HLRCC patients and underscore conserved molecular alterations correlating with inactivation of the FH tumor suppressor gene.Nicholas W. BatemanChristopher M. TarneyTamara AbulezAnthony R. SoltisMing ZhouKelly ConradsTracy LitziJulie OliverBrian HoodPaul DriggersCoralie ViolletClifton DalgardMatthew WilkersonWilliam CatherinoChad A. HamiltonKathleen M. DarcyYovanni CasablancaAyman Al-HendyJames SegarsThomas P. ConradsG. Larry MaxwellNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicholas W. Bateman Christopher M. Tarney Tamara Abulez Anthony R. Soltis Ming Zhou Kelly Conrads Tracy Litzi Julie Oliver Brian Hood Paul Driggers Coralie Viollet Clifton Dalgard Matthew Wilkerson William Catherino Chad A. Hamilton Kathleen M. Darcy Yovanni Casablanca Ayman Al-Hendy James Segars Thomas P. Conrads G. Larry Maxwell Proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients
description	Abstract 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 < 0.0001). These results confirm and define novel proteogenomic alterations in uterine leiomyoma tissues collected from HLRCC patients and underscore conserved molecular alterations correlating with inactivation of the FH tumor suppressor gene.
format	article
author	Nicholas W. Bateman Christopher M. Tarney Tamara Abulez Anthony R. Soltis Ming Zhou Kelly Conrads Tracy Litzi Julie Oliver Brian Hood Paul Driggers Coralie Viollet Clifton Dalgard Matthew Wilkerson William Catherino Chad A. Hamilton Kathleen M. Darcy Yovanni Casablanca Ayman Al-Hendy James Segars Thomas P. Conrads G. Larry Maxwell
author_facet	Nicholas W. Bateman Christopher M. Tarney Tamara Abulez Anthony R. Soltis Ming Zhou Kelly Conrads Tracy Litzi Julie Oliver Brian Hood Paul Driggers Coralie Viollet Clifton Dalgard Matthew Wilkerson William Catherino Chad A. Hamilton Kathleen M. Darcy Yovanni Casablanca Ayman Al-Hendy James Segars Thomas P. Conrads G. Larry Maxwell
author_sort	Nicholas W. Bateman
title	Proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients
title_short	Proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients
title_full	Proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients
title_fullStr	Proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients
title_full_unstemmed	Proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients
title_sort	proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c023cf0dac914100a5bb9c69090f4b69
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Proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients

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