A Variant in a MicroRNA complementary site in the 3′ UTR of the KIT oncogene increases risk of acral melanoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-03

AUTHORS

Sirie E. Godshalk, Trupti Paranjape, Sunitha Nallur, William Speed, Elcie Chan, Annette M. Molinaro, Antonella Bacchiocchi, Kathleen Hoyt, Kathryn Tworkoski, David F. Stern, Mario Sznol, Stephan Ariyan, Rossitza Lazova, Ruth Halaban, Kenneth K. Kidd, Joanne Weidhaas, Frank J. Slack

ABSTRACT

MicroRNAs (miRNAs) are small ∼22nt single stranded RNAs that negatively regulate protein expression by binding to partially complementary sequences in the 3' untranslated region (3' UTRs) of target gene messenger RNAs (mRNA). Recently, mutations have been identified in both miRNAs and target genes that disrupt regulatory relationships, contribute to oncogenesis and serve as biomarkers for cancer risk. KIT, an established oncogene with a multifaceted role in melanogenesis and melanoma pathogenesis, has recently been shown to be upregulated in some melanomas, and is also a target of the miRNA miR-221. Here, we describe a genetic variant in the 3' UTR of the KIT oncogene that correlates with a greater than fourfold increased risk of acral melanoma. This KIT variant results in a mismatch in the seed region of a miR-221 complementary site and reporter data suggests that this mismatch can result in increased expression of the KIT oncogene. Consistent with the hypothesis that this is a functional variant, KIT mRNA and protein levels are both increased in the majority of samples harboring the KIT variant. This work identifies a novel genetic marker for increased heritable risk of melanoma. More... »

PAGES

1542

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/onc.2010.536

DOI

http://dx.doi.org/10.1038/onc.2010.536

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1032596296

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21119596


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