Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0278883 (
metastatic melanoma
)
6,224
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A progressive increase in copy number variation (CNV) characterizes the natural history of cutaneous melanoma progression toward later disease stages, but our understanding of genetic drivers underlying chromosomal arm-level CNVs remains limited. To identify candidate progression drivers, we mined the TCGA SKCM dataset and identified
HDGF
as a recurrently amplified gene whose high mRNA expression correlates with poor patient survival. Using melanocyte-specific overexpression in the zebrafish BRAF
V600E
-driven MiniCoopR melanoma model, we show that
HDGF
accelerates melanoma development in vivo. Transcriptional analysis of
HDGF
compared to control EGFP tumors showed the activation of endothelial/angiogenic pathways. We validated this observation using an endothelial kdrl:mCherry reporter line which showed
HDGF
to increases tumor vasculature.
HDGF
is frequently co-altered with the established melanoma driver SETDB1. Both genes are located on chromosome 1q, and their co-amplification is observed in up to 13% of
metastatic melanoma
. TCGA patients with both genes amplified and/or overexpressed have a worse melanoma specific survival. We tested co-expression of
HDGF
and SETDB1 in the MiniCoopR model, which resulted in faster and more aggressive melanoma development than either gene individually. Our work identifies the co-amplification of
HDGF
and SETDB1 as a functional driver of melanoma progression and poor patient prognosis.
...
PMID:Recurrent co-alteration of HDGF and SETDB1 on chromosome 1q drives cutaneous melanoma progression and poor prognosis. 3306 82
