PXD017743 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
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] |
Keyword List
submitter keyword: uveal melanoma, metastasis, BAP1 |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD017743
- Label: PRIDE project
- Name: Molecular profiling of driver events in metastatic uveal melanoma