It appears you don't have support to open PDFs in this web browser. To view this file, Open with your PDF reader
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.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details
1 Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525); Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, The John P. Murtha Cancer Center, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525); Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Bethesda, USA (GRID:grid.201075.1) (ISNI:0000 0004 0614 9826)
2 Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525)
3 Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525); Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Bethesda, USA (GRID:grid.201075.1) (ISNI:0000 0004 0614 9826)
4 Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Bethesda, USA (GRID:grid.201075.1) (ISNI:0000 0004 0614 9826); Uniformed Services University of the Health Sciences, The American Genome Center, Department of Anatomy, Physiology, and Genetics, Collaborative Health Initiative Research Program, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525)
5 Inova Health System, Women’s Health Integrated Research Center, Women’s Service Line, Falls Church, USA (GRID:grid.414629.c) (ISNI:0000 0004 0401 0871)
6 Johns Hopkins University School of Medicine, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311)
7 Uniformed Services University of the Health Sciences, The American Genome Center, Department of Anatomy, Physiology, and Genetics, Collaborative Health Initiative Research Program, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525)
8 Uniformed Services University of the Health Sciences, Department of Gynecologic Surgery and Obstetrics, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525)
9 Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525); Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, The John P. Murtha Cancer Center, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525)
10 University of Illinois College of Medicine, Chicago, USA (GRID:grid.185648.6) (ISNI:0000 0001 2175 0319)
11 Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525); Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, The John P. Murtha Cancer Center, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525); Inova Health System, Women’s Health Integrated Research Center, Women’s Service Line, Falls Church, USA (GRID:grid.414629.c) (ISNI:0000 0004 0401 0871); Annandale, USA (GRID:grid.414629.c)
12 Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525); Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, The John P. Murtha Cancer Center, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525); Inova Health System, Women’s Health Integrated Research Center, Women’s Service Line, Falls Church, USA (GRID:grid.414629.c) (ISNI:0000 0004 0401 0871)