Proteomics

Dataset Information

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MITF deficiency accelerates GNAQ-driven uveal melanoma


ABSTRACT: Cutaneous melanoma (CM) and uveal melanoma (UM) both originate from the melanocytic lineage but are primarily driven by distinct oncogenic drivers, BRAF/NRAS or GNAQ/GNA11 respectively. The melanocytic master transcriptional regulator, MITF, is essential for both CM development and maintenance, but its role in UM is largely unexplored. Here, we use zebrafish models to dissect the key UM oncogenic signaling events, and establish the role of MITF in UM tumors. Remarkably, mitfa deficiency was profoundly UM promoting, dramatically accelerating the onset and progression of tumors induced by Tg(mitfa:GNAQQ209L);tp53M214K/M214K. To further explore the role of MITF in GNAQ-driven tumorigenesis, we performed phospho-proteomics and total proteomics on 5 zebrafish GNAQ Tg(mitfa:GNAQQ209L);tp53M214K/M214K tumors and 5 zebrafish GNAQ Tg(mitfa:GNAQQ209L);tp53M214K/M214K;mitfa-/- tumors.

INSTRUMENT(S): Orbitrap Exploris 240

ORGANISM(S): Danio Rerio (zebrafish) (brachydanio Rerio)

TISSUE(S): Melanocyte, Melanoma Cell

DISEASE(S): Uveal Melanoma

SUBMITTER: Grace Phelps  

LAB HEAD: Jacqueline A. Lees

PROVIDER: PXD030527 | Pride | 2023-03-11

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
1005_GA_10plex_nonPhospho.mzML Mzml
1005_GA_10plex_nonPhospho.mzid.gz Mzid
1005_GP_FT.mzML Mzml
1005_GP_FT.mzid.gz Mzid
checksum.txt Txt
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Publications

MITF deficiency accelerates GNAQ-driven uveal melanoma.

Phelps Grace B GB   Hagen Hannah R HR   Amsterdam Adam A   Lees Jacqueline A JA  

Proceedings of the National Academy of Sciences of the United States of America 20220505 19


Cutaneous melanoma (CM) and uveal melanoma (UM) both originate from the melanocytic lineage but are primarily driven by distinct oncogenic drivers, BRAF/NRAS or GNAQ/GNA11, respectively. The melanocytic master transcriptional regulator, MITF, is essential for both CM development and maintenance, but its role in UM is largely unexplored. Here, we use zebrafish models to dissect the key UM oncogenic signaling events and establish the role of MITF in UM tumors. Using a melanocytic lineage expressio  ...[more]

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