Imperial College London

ProfessorAnneBowcock

Faculty of MedicineNational Heart & Lung Institute

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 1511a.bowcock

 
 
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Location

 

Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Field:2016:10.18632/oncotarget.10962,
author = {Field, MG and Durante, MA and Decatur, CL and Tarlan, B and Oelschlager, KM and Stone, JF and Kuznetsov, J and Bowcock, AM and Kurtenbach, S and Harbour, JW},
doi = {10.18632/oncotarget.10962},
journal = {Oncotarget},
pages = {59209--59219},
title = {Epigenetic reprogramming and aberrant expression of PRAME are associated with increased metastatic risk in Class 1 and Class 2 uveal melanomas.},
url = {http://dx.doi.org/10.18632/oncotarget.10962},
volume = {7},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - BACKGROUND: We previously identified PRAME as a biomarker for metastatic risk in Class 1 uveal melanomas. In this study, we sought to define a threshold value for positive PRAME expression (PRAME+) in a large dataset, identify factors associated with PRAME expression, evaluate the prognostic value of PRAME in Class 2 uveal melanomas, and determine whether PRAME expression is associated with aberrant hypomethylation of the PRAME promoter. RESULTS: Among 678 samples analyzed by qPCR, 498 (73.5%) were PRAME- and 180 (26.5%) were PRAME+. Class 1 tumors were more likely to be PRAME-, whereas Class 2 tumors were more likely to be PRAME+ (P < 0.0001). PRAME expression was associated with shorter time to metastasis and melanoma specific mortality in Class 2 tumors (P = 0.01 and P = 0.02, respectively). In Class 1 tumors, PRAME expression was directly associated with SF3B1 mutations (P < 0.0001) and inversely associated with EIF1AX mutations (P = 0.004). PRAME expression was strongly associated with hypomethylation at 12 CpG sites near the PRAME promoter. MATERIALS AND METHODS: Analyses included PRAME mRNA expression, Class 1 versus Class 2 status, chromosomal copy number, mutation status of BAP1, EIF1AX, GNA11, GNAQ and SF3B1, and genomic DNA methylation status. Analyses were performed on 555 de-identified samples from Castle Biosciences, 123 samples from our center, and 80 samples from the TCGA. CONCLUSIONS: PRAME is aberrantly hypomethylated and activated in Class 1 and Class 2 uveal melanomas and is associated with increased metastatic risk in both classes. Since PRAME has been successfully targeted for immunotherapy, it may prove to be a companion prognostic biomarker.
AU - Field,MG
AU - Durante,MA
AU - Decatur,CL
AU - Tarlan,B
AU - Oelschlager,KM
AU - Stone,JF
AU - Kuznetsov,J
AU - Bowcock,AM
AU - Kurtenbach,S
AU - Harbour,JW
DO - 10.18632/oncotarget.10962
EP - 59219
PY - 2016///
SN - 1949-2553
SP - 59209
TI - Epigenetic reprogramming and aberrant expression of PRAME are associated with increased metastatic risk in Class 1 and Class 2 uveal melanomas.
T2 - Oncotarget
UR - http://dx.doi.org/10.18632/oncotarget.10962
UR - http://hdl.handle.net/10044/1/52552
VL - 7
ER -