PXD030217

PXD030217 is an original dataset announced via ProteomeXchange.

Title	Oncogenic mutations in the Gα-protein GNA11 convey a shorter disease specific survival and are more strongly associated with loss of BAP1 and chromosomal alterations than GNAQ mutations in uveal melanoma
Description	Mutations of the Gα-proteins GNAQ and GNA11 are found in 85-90% of uveal melanomas (UMs). We analyzed the association of GNAQ and GNA11 mutations with disease-specific survival, gene expression profiles, and cytogenetic alterations in 219 UMs. Our analysis showed a shorter disease-specific survival of GNA11 mutated cases as compared to those carrying a GNAQ mutation (median months: 26.97 [95% CI 25.02-37.08], vs not reached, p=0.058; HR=1.97 [95%CI 1.12-3.46], p=0.02). The GNA11 mutation was associated with expression alterations of the BRCA1-associated protein 1 (BAP1; p=0.0005), chr3 monosomy (p=0.0002), chr8q amplification (p=0.038), the combination of the latter two (p=0.0002), and, inversely, with chr6p amplification (p=0.003). We used tandem-affinity-purification and mass spectrometry to show that the two G-proteins have different protein interaction partners. The Tet Methylcytosine Dioxygenase 2, TET2, a protein that is involved in DNA-demethylation, physically interacts with GNAQ but not with GNA11 as confirmed by immunoprecipitation analyses. High risk UM shows a clearly different DNA-methylation pattern and different control of DNA-methylation by the two G-proteins might, at least in part, explain the different association with UM progression.
HostingRepository	PRIDE
AnnounceDate	2022-06-22
AnnouncementXML	Submission_2022-06-22_06:23:25.338.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Martina Bartolucci
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-06 09:01:23	ID requested
⏵ 1	2022-06-22 06:23:26	announced

Piaggio F, Croce M, Reggiani F, Monti P, Bernardi C, Ambrosio M, Banelli B, Dogrus, ö, z M, Jockers R, Bordo D, Puzone R, Viaggi S, Coviello D, Lanza FB, Bartolucci M, Petretto A, Mosci C, Gangemi R, van der Velden PA, Jager MJ, Pfeffer U, Amaro A, -protein GNAQ mutations. Eur J Cancer, 170():27-41(2022) [pubmed]

submitter keyword: metastasis risk, GNAQ, GNA11, BAP1, ASAP1

Andrea Petretto
contact affiliation	IRCCS Istituto Giannina Gaslini
contact email	a.petretto@gmail.com
lab head
Martina Bartolucci
contact affiliation	IRCCS Gaslini
contact email	smartibartolucci@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD030217
     1. Label: PRIDE project
     2. Name: Oncogenic mutations in the Gα-protein GNA11 convey a shorter disease specific survival and are more strongly associated with loss of BAP1 and chromosomal alterations than GNAQ mutations in uveal melanoma