title: MicroRNA signatures differentiate melanoma subtypes.
abstract: Melanoma is an aggressive cancer that is highly resistance to therapies once metastasized. We studied microRNA (miRNA) expression in clinical melanoma subtypes and evaluated different miRNA signatures in the background of gain of function somatic and inherited mutations associated with melanoma. Total RNA from 42 patient derived primary melanoma cell lines and three independent normal primary melanocyte cell cultures was evaluated by miRNA array. MiRNA expression was then analyzed comparing subtypes and additional clinicopathologic criteria including somatic mutations. The prevalence and association of an inherited variant in a miRNA binding site in the 3'UTR of the KRAS oncogene, referred to as the KRAS-variant, was also evaluated. We show that seven miRNAs, miR-142-3p, miR-486, miR-214, miR-218, miR-362, miR-650 and miR-31, were significantly correlated with acral as compared to non-acral melanomas (p < 0.04). In addition, we discovered that the KRAS-variant was enriched in non-acral melanoma (25%), and that miR-137 under expression was significantly associated with melanomas with the KRAS-variant. Our findings indicate that miRNAs are differentially expressed in melanoma subtypes and that their misregulation can be impacted by inherited gene variants, supporting the hypothesis that miRNA misregulation reflects biological differences in melanoma.
authors.affiliation: Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Elcie
authors.initials: E
authors.lastname: Chan
authors.forename: Rajeshvari
authors.initials: R
authors.lastname: Patel
authors.forename: Sunitha
authors.initials: S
authors.lastname: Nallur
authors.forename: Elena
authors.initials: E
authors.lastname: Ratner
authors.forename: Antonella
authors.initials: A
authors.lastname: Bacchiocchi
authors.forename: Kathleen
authors.initials: K
authors.lastname: Hoyt
authors.forename: Sebastian
authors.initials: S
authors.lastname: Szpakowski
authors.forename: Sirie
authors.initials: S
authors.lastname: Godshalk
authors.forename: Stephan
authors.initials: S
authors.lastname: Ariyan
authors.forename: Mario
authors.initials: M
authors.lastname: Sznol
authors.forename: Ruth
authors.initials: R
authors.lastname: Halaban
authors.forename: Michael
authors.initials: M
authors.lastname: Krauthammer
authors.forename: David
authors.initials: D
authors.lastname: Tuck
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Slack
authors.forename: Joanne Barnes
authors.initials: JB
authors.lastname: Weidhaas
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000032:analysis*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012334:RNA, Neoplasm / Q000032:analysis; D018631:ras Proteins / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C117307:KRAS protein, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins