Genes, chromosomes & cancer · 2007
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.
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Pujana Miguel Angel, Ruiz Anna, Badenas Cèlia, Puig-Butille Josep-Anton, Nadal Marga, Stark Mitchell, Gómez Laia, Valls Joan, Solé Xavier, Hernández Pilar, Cerrato Celia, Madrigal Irene, de Cid Rafael, Aguilar Helena, Capellá Gabriel, Cal Santiago, James Michael R, Walker Graeme J, Malvehy Josep, Milà Montserrat, Hayward Nicholas K, Estivill Xavier, Puig Susana
Аннотация
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.