title: The CASC15 Long Intergenic Noncoding RNA Locus Is Involved in Melanoma Progression and Phenotype Switching.
abstract: In recent years, considerable advances have been made in the characterization of protein-coding alterations involved in the pathogenesis of melanoma. However, despite their growing implication in cancer, little is known about the role of long noncoding RNAs in melanoma progression. We hypothesized that copy number alterations (CNAs) of intergenic nonprotein-coding domains could help identify long intergenic noncoding RNAs (lincRNAs) associated with metastatic cutaneous melanoma. Among several candidates, our approach uncovered the chromosome 6p22.3 CASC15 (cancer susceptibility candidate 15) lincRNA locus as a frequently gained genomic segment in metastatic melanoma tumors and cell lines. The locus was actively transcribed in metastatic melanoma cells, and upregulation of CASC15 expression was associated with metastatic progression to brain metastasis in a mouse xenograft model. In clinical specimens, CASC15 levels increased during melanoma progression and were independent predictors of disease recurrence in a cohort of 141 patients with AJCC (American Joint Committee on Cancer) stage III lymph node metastasis. Moreover, small interfering RNA (siRNA) knockdown experiments revealed that CASC15 regulates melanoma cell phenotype switching between proliferative and invasive states. Accordingly, CASC15 levels correlated with known gene signatures corresponding to melanoma proliferative and invasive phenotypes. These findings support a key role for CASC15 in metastatic melanoma.
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, California, USA.
authors.forename: Laurent
authors.initials: L
authors.lastname: Lessard
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, California, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, California, USA.
authors.forename: Diego M
authors.initials: DM
authors.lastname: Marzese
authors.affiliation: Advanced Cell Diagnostics, Hayward, California, USA.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, California, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Chong
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, California, USA.
authors.forename: Neal
authors.initials: N
authors.lastname: Kawas
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, California, USA.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Donovan
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, California, USA.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kiyohara
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, California, USA.
authors.forename: Sandy
authors.initials: S
authors.lastname: Hsu
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, California, USA.
authors.forename: Nellie
authors.initials: N
authors.lastname: Nelson
authors.affiliation: Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Sivan
authors.initials: S
authors.lastname: Izraely
authors.affiliation: Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Sagi-Assif
authors.affiliation: Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Isaac P
authors.initials: IP
authors.lastname: Witz
authors.affiliation: Advanced Cell Diagnostics, Hayward, California, USA.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Ma
authors.affiliation: Advanced Cell Diagnostics, Hayward, California, USA.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, California, USA. Electronic address: hoond@jwci.org.
authors.forename: Dave S B
authors.initials: DSB
authors.lastname: Hoon
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D056426:Genetic Loci / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008544:Melanocytes / Q000473:pathology; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D010641:Phenotype; D062085:RNA, Long Noncoding / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D062085:RNA, Long Noncoding