PXD024830

PXD024830 is an original dataset announced via ProteomeXchange.

Title	Proteogenomic Landscape of Uterine Leiomyomas from Hereditary Leiomyomatosis and Renal Cell Cancer Patients
Description	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.
HostingRepository	PRIDE
AnnounceDate	2021-12-15
AnnouncementXML	Submission_2021-12-15_03:29:23.368.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Brian Hood
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-18 03:54:59	ID requested
⏵ 1	2021-12-15 03:29:23	announced

Dataset with its publication pending

submitter keyword: Hereditary Leiomyomatosis and Renal Cell Cancer, HLRCC, Uterine Leiomyoma, Fibroid, Proteogenomics, TMT-10, Quantitative Proteomics

Thomas P Conrads, PhD
contact affiliation	Director of Women’s Health Research Women’s Service Line Inova Health System Chief Scientific Officer Gynecologic Cancer Center of Excellence John P. Murtha Cancer Center Research Program Uniformed Services University of the Health Sciences
contact email	conrads@whirc.org
lab head
Brian Hood
contact affiliation	Women's Health Integrated Research Center
contact email	hoodb@whirc.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024830
     1. Label: PRIDE project
     2. Name: Proteogenomic Landscape of Uterine Leiomyomas from Hereditary Leiomyomatosis and Renal Cell Cancer Patients