PXD017743

PXD017743 is an original dataset announced via ProteomeXchange.

Title	Molecular profiling of driver events in metastatic uveal melanoma
Description	Uveal melanoma (UM) is a rare form of melanoma with a genetics and immunology that is different from skin melanoma. Previous studies have identified genetic driver events of early stage disease when the tumor is confined to the eye. In this study, we have characterized genomic events in UM metastases using whole-genome and RNA sequencing from thirty-two and twenty-eight patients, respectively, and profiled individual tumor infiltrating lymphocytes in a number of the metastases. We find that 91% of the patients have metastases carrying inactivating events in the tumor suppressor BAP1 and this coincided with somatic alterations in GNAQ, GNA11, CYSLTR2, PLCB4, SF3B1 and/or CDKN2A. Mutational signature analysis revealed a rare subset of tumors with prominent signs of UV damage, associated with outlier mutational burden. We study copy number variations (CNV) and find overrepresented events, some of which were not altered in matched primary eye tumors. A focused siRNA screen identified functionally significant genes of some of the segments recurrently gained. We reintroduced a functional copy of BAP1 into a patient-derived BAP1 deficient tumor cell line and found broad transcriptomic changes of genes associated with subtype distinction and prognosis in primary UM. Lastly, our analysis of the immune microenvironments of metastases revealed a presence of tumor-reactive T cells. However, a large fraction expressed the immune checkpoint receptors such as TIM-3, TIGIT and LAG3. These results provide an updated view of genomic events represented in metastatic UM and immune interactions in advanced lesions.
HostingRepository	PRIDE
AnnounceDate	2020-03-18
AnnouncementXML	Submission_2020-04-30_03:29:53.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Evelin Berger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue; monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-02-26 02:58:45	ID requested
1	2020-03-18 04:56:18	announced
⏵ 2	2020-04-30 03:32:06	announced	2020-04-30: Updated publication reference for PubMed record(s): 32313009.

Karlsson J, Nilsson LM, Mitra S, Als, é, n S, Shelke GV, Sah VR, Forsberg EMV, Stierner U, All-Eriksson C, Einarsdottir B, Jespersen H, Ny L, Lindn, é, r P, Larsson E, Olofsson Bagge R, Nilsson JA, Molecular profiling of driver events in metastatic uveal melanoma. Nat Commun, 11(1):1894(2020) [pubmed]

submitter keyword: uveal melanoma, metastasis, BAP1

Carina Sihlbom
contact affiliation	Proteomics Core Facility, University of Gothenburg, Sweden
contact email	carina.sihlbom@gu.se
lab head
Evelin Berger
contact affiliation	University of Gothenburg
contact email	evelin.berger@gu.se
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/03/PXD017743

PRIDE project URI

• PRIDE
  1. PXD017743
     1. Label: PRIDE project
     2. Name: Molecular profiling of driver events in metastatic uveal melanoma