PXD027968

PXD027968 is an original dataset announced via ProteomeXchange.

Title	Anatomic position determines oncogenic specificity in melanoma
Description	Oncogenic alterations to DNA are not transforming in all cellular contexts. This may be due to pre-existing transcriptional programs in the cell of origin. Here, we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet, or under the nails. We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma but CRKL amplifications in acral melanoma. We modeled these changes in transgenic zebrafish models and found that CRKL-driven tumors predominantly formed in the fins of the fish. The fins are the evolutionary precursors to tetrapod limbs, indicating that melanocytes in these acral locations may be uniquely susceptible to CRKL. RNA profiling of these fin/limb melanocytes, compared to body melanocytes, revealed a positional identity gene program typified by posterior HOX13 genes. This positional gene program synergized with CRKL to drive tumors at acral sites. Abrogation of this CRKL-driven program eliminated the anatomic specificity of acral melanoma. These data suggest that the anatomic position of the cell of origin endows it with a unique transcriptional state that makes it susceptible to only certain oncogenic insults.
HostingRepository	PRIDE
AnnounceDate	2022-01-12
AnnouncementXML	Submission_2022-05-06_09:10:10.719.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pavel Shliaha
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-17 04:05:34	ID requested
1	2022-01-12 02:34:47	announced
⏵ 2	2022-05-06 09:10:11	announced	2022-05-06: Updated publication reference for PubMed record(s): 35355015.

Weiss JM, Hunter MV, Cruz NM, Baggiolini A, Tagore M, Ma Y, Misale S, Marasco M, Simon-Vermot T, Campbell NR, Newell F, Wilmott JS, Johansson PA, Thompson JF, Long GV, Pearson JV, Mann GJ, Scolyer RA, Waddell N, Montal ED, Huang TH, Jonsson P, Donoghue MTA, Harris CC, Taylor BS, Xu T, Chalign, é R, Shliaha PV, Hendrickson R, Jungbluth AA, Lezcano C, Koche R, Studer L, Ariyan CE, Solit DB, Wolchok JD, Merghoub T, Rosen N, Hayward NK, White RM, Anatomic position determines oncogenic specificity in melanoma. Nature, 604(7905):354-361(2022) [pubmed]

submitter keyword: IP-MS, human, melanoma

Ronald Hendrickson
contact affiliation	Microchemistry and Proteomics Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
contact email	hendricr@mskcc.org
lab head
Pavel Shliaha
contact affiliation	Syddansk University
contact email	pavels@bmb.sdu.dk
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/2022/01/PXD027968

PRIDE project URI

• PRIDE
  1. PXD027968
     1. Label: PRIDE project
     2. Name: Anatomic position determines oncogenic specificity in melanoma