title: Molecular characterization of a t(9;12)(p21;q13) balanced chromosome translocation in combination with integrative genomics analysis identifies C9orf14 as a candidate tumor-suppressor.
abstract: A large number of nevi (LNN) is a high risk phenotypic trait for developing cutaneous malignant melanoma (CMM). In this study, the breakpoints of a t(9;12)(p21;q13) balanced chromosome translocation were finely mapped in a family with LNN and CMM. Molecular characterization of the 9p21 breakpoint identified a novel gene C9orf14 expressed in melanocytes disrupted by the translocation. Integrative analysis of functional genomics data was applied to determine the role of C9orf14 in CMM development. An analysis of genome-wide DNA copy number alterations in melanoma tumors revealed the loss of the C9orf14 locus, located proximal to CDKN2A, in approximately one-fourth of tumors. Analysis of gene expression data in cancer cell lines and melanoma tumors suggests a loss of C9orf14 expression in melanoma tumorigenesis. Taken together, our results indicate that C9orf14 is a candidate tumor-suppressor for nevus development and late stage melanoma at 9p21, a region frequently deleted in different types of human cancers.
authors.affiliation: Bioinformatics and Biostatistics Unit, Translational Research Laboratory, Catalan Institute of Oncology, IDIBELL, L'Hospitalet, Barcelona, Spain. mapujana@ico.scs.es
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Pujana
authors.forename: Anna
authors.initials: A
authors.lastname: Ruiz
authors.forename: Cèlia
authors.initials: C
authors.lastname: Badenas
authors.forename: Josep-Anton
authors.initials: JA
authors.lastname: Puig-Butille
authors.forename: Marga
authors.initials: M
authors.lastname: Nadal
authors.forename: Mitchell
authors.initials: M
authors.lastname: Stark
authors.forename: Laia
authors.initials: L
authors.lastname: Gómez
authors.forename: Joan
authors.initials: J
authors.lastname: Valls
authors.forename: Xavier
authors.initials: X
authors.lastname: Solé
authors.forename: Pilar
authors.initials: P
authors.lastname: Hernández
authors.forename: Celia
authors.initials: C
authors.lastname: Cerrato
authors.forename: Irene
authors.initials: I
authors.lastname: Madrigal
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cid
authors.forename: Helena
authors.initials: H
authors.lastname: Aguilar
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capellá
authors.forename: Santiago
authors.initials: S
authors.lastname: Cal
authors.forename: Michael R
authors.initials: MR
authors.lastname: James
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Walker
authors.forename: Josep
authors.initials: J
authors.lastname: Malvehy
authors.forename: Montserrat
authors.initials: M
authors.lastname: Milà
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
authors.forename: Susana
authors.initials: S
authors.lastname: Puig
mesh_terms: D002881:Chromosomes, Human, Pair 12; D002899:Chromosomes, Human, Pair 9; D016147:Genes, Tumor Suppressor; D006801:Humans; D008545:Melanoma / Q000235:genetics; D009506:Nevus / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics; D014178:Translocation, Genetic