title: Histology-specific microRNA alterations in melanoma.
abstract: We examined the microRNA signature that distinguishes the most common melanoma histological subtypes, superficial spreading melanoma (SSM) and nodular melanoma (NM). We also investigated the mechanisms underlying the differential expression of histology-specific microRNAs. MicroRNA array performed on a training cohort of 82 primary melanoma tumors (26 SSM, 56 NM), and nine congenital nevi (CN) revealed 134 microRNAs differentially expressed between SSM and NM (P<0.05). Out of 134 microRNAs, 126 remained significant after controlling for thickness and 31 were expressed at a lower level in SSM compared with both NM and CN. For seven microRNAs (let-7g, miR-15a, miR-16, miR-138, miR-181a, miR-191, and miR-933), the downregulation was associated with selective genomic loss in SSM cell lines and primary tumors, but not in NM cell lines and primary tumors. The lower expression level of six out of seven microRNAs in SSM compared with NM was confirmed by real-time PCR on a subset of cases in the training cohort and validated in an independent cohort of 97 melanoma cases (38 SSM, 59 NM). Our data support a molecular classification in which SSM and NM are two molecularly distinct phenotypes. Therapeutic strategies that take into account subtype-specific alterations might improve the outcome of melanoma patients.
authors.affiliation: The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Poliseno
authors.forename: Adele
authors.initials: A
authors.lastname: Haimovic
authors.forename: Miguel F
authors.initials: MF
authors.lastname: Segura
authors.forename: Douglas
authors.initials: D
authors.lastname: Hanniford
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Christos
authors.forename: Farbod
authors.initials: F
authors.lastname: Darvishian
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.forename: Richard L
authors.initials: RL
authors.lastname: Shapiro
authors.forename: Anna C
authors.initials: AC
authors.lastname: Pavlick
authors.forename: Russell S
authors.initials: RS
authors.lastname: Berman
authors.forename: Eva
authors.initials: E
authors.lastname: Hernando
authors.forename: Jiri
authors.initials: J
authors.lastname: Zavadil
authors.forename: Iman
authors.initials: I
authors.lastname: Osman
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011446:Prospective Studies
chemical_list: D035683:MicroRNAs