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

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

doi:10.1038/s41598-021-88585-x

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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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.

Original language	English
Article number	9371
Journal	Scientific Reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-021-88585-x
State	Published - Dec 2021
Externally published	Yes

Access to Document

10.1038/s41598-021-88585-x

Cite this

Bateman, N. W., Tarney, C. M., Abulez, T., Soltis, A. R., Zhou, M., Conrads, K., Litzi, T., Oliver, J., Hood, B., Driggers, P., Viollet, C., Dalgard, C., Wilkerson, M., Catherino, W., Hamilton, C. A., Darcy, K. M., Casablanca, Y., Al-Hendy, A., Segars, J., ... Larry Maxwell, G. (2021). Proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients. Scientific Reports, 11(1), Article 9371. https://doi.org/10.1038/s41598-021-88585-x

@article{11484c6297934245802d2fff4e665e5b,

title = "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) 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.",

author = "Bateman, {Nicholas W.} and Tarney, {Christopher M.} and Tamara Abulez and Soltis, {Anthony R.} and Ming Zhou and Kelly Conrads and Tracy Litzi and Julie Oliver and Brian Hood and Paul Driggers and Coralie Viollet and Clifton Dalgard and Matthew Wilkerson and William Catherino and Hamilton, {Chad A.} and Darcy, {Kathleen M.} and Yovanni Casablanca and Ayman Al-Hendy and James Segars and Conrads, {Thomas P.} and {Larry Maxwell}, G.",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

doi = "10.1038/s41598-021-88585-x",

language = "English",

volume = "11",

journal = "Scientific Reports",

issn = "2045-2322",

number = "1",

}

Bateman, NW, Tarney, CM, Abulez, T, Soltis, AR, Zhou, M, Conrads, K, Litzi, T, Oliver, J, Hood, B, Driggers, P, Viollet, C, Dalgard, C, Wilkerson, M, Catherino, W, Hamilton, CA, Darcy, KM , Casablanca, Y, Al-Hendy, A, Segars, J, Conrads, TP & Larry Maxwell, G 2021, 'Proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients', Scientific Reports, vol. 11, no. 1, 9371. https://doi.org/10.1038/s41598-021-88585-x

TY - JOUR

T1 - Proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients

AU - Bateman, Nicholas W.

AU - Tarney, Christopher M.

AU - Abulez, Tamara

AU - Soltis, Anthony R.

AU - Zhou, Ming

AU - Conrads, Kelly

AU - Litzi, Tracy

AU - Oliver, Julie

AU - Hood, Brian

AU - Driggers, Paul

AU - Viollet, Coralie

AU - Dalgard, Clifton

AU - Wilkerson, Matthew

AU - Catherino, William

AU - Hamilton, Chad A.

AU - Darcy, Kathleen M.

AU - Casablanca, Yovanni

AU - Al-Hendy, Ayman

AU - Segars, James

AU - Conrads, Thomas P.

AU - Larry Maxwell, G.

PY - 2021/12

Y1 - 2021/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85105240095&partnerID=8YFLogxK

U2 - 10.1038/s41598-021-88585-x

DO - 10.1038/s41598-021-88585-x

M3 - Article

C2 - 33931688

AN - SCOPUS:85105240095

SN - 2045-2322

VL - 11

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 9371

ER -

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

Abstract

Access to Document

Fingerprint

Cite this