title: CASC15-S Is a Tumor Suppressor lncRNA at the 6p22 Neuroblastoma Susceptibility Locus.
abstract: Chromosome 6p22 was identified recently as a neuroblastoma susceptibility locus, but its mechanistic contributions to tumorigenesis are as yet undefined. Here we report that the most highly significant single-nucleotide polymorphism (SNP) associations reside within CASC15, a long noncoding RNA that we define as a tumor suppressor at 6p22. Low-level expression of a short CASC15 isoform (CASC15-S) associated highly with advanced neuroblastoma and poor patient survival. In human neuroblastoma cells, attenuating CASC15-S increased cellular growth and migratory capacity. Gene expression analysis revealed downregulation of neuroblastoma-specific markers in cells with attenuated CASC15-S, with concomitant increases in cell adhesion and extracellular matrix transcripts. Altogether, our results point to CASC15-S as a mediator of neural growth and differentiation, which impacts neuroblastoma initiation and progression.
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Mike R
authors.initials: MR
authors.lastname: Russell
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Annalise
authors.initials: A
authors.lastname: Penikis
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Derek A
authors.initials: DA
authors.lastname: Oldridge
authors.affiliation: Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Alvarez-Dominguez
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Lee
authors.initials: L
authors.lastname: McDaniel
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Maura
authors.initials: M
authors.lastname: Diamond
authors.affiliation: Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Olivia
authors.initials: O
authors.lastname: Padovan
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. Center for Biomedical Informatics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Pichai
authors.initials: P
authors.lastname: Raman
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Yimei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Oncogenomics Section, Genetics Branch, Center for Cancer Research, NCI, Bethesda, Maryland.
authors.forename: Jun S
authors.initials: JS
authors.lastname: Wei
authors.affiliation: Oncogenomics Section, Genetics Branch, Center for Cancer Research, NCI, Bethesda, Maryland.
authors.forename: Shile
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Division of Hematology-Oncology, Children's Hospital Los Angeles and Saban Research Institute, University of Southern California, Los Angeles, California.
authors.forename: Janahan
authors.initials: J
authors.lastname: Gnanchandran
authors.affiliation: Department of Pediatrics, Division of Hematology-Oncology, Children's Hospital Los Angeles and Saban Research Institute, University of Southern California, Los Angeles, California.
authors.forename: Robert
authors.initials: R
authors.lastname: Seeger
authors.affiliation: Department of Pediatrics, Division of Hematology-Oncology, Children's Hospital Los Angeles and Saban Research Institute, University of Southern California, Los Angeles, California.
authors.forename: Shahab
authors.initials: S
authors.lastname: Asgharzadeh
authors.affiliation: Oncogenomics Section, Genetics Branch, Center for Cancer Research, NCI, Bethesda, Maryland.
authors.forename: Javed
authors.initials: J
authors.lastname: Khan
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. The Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Diskin
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. The Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: John M
authors.initials: JM
authors.lastname: Maris
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. The Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. colek@email.chop.edu.
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Cole
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding / Q000235:genetics*; D015203:Reproducibility of Results
chemical_list: D062085:RNA, Long Noncoding