title: Tumor suppressor genes FHIT and WWOX are deleted in primary effusion lymphoma (PEL) cell lines.
abstract: Primary effusion lymphoma (PEL) is a diffuse-large B-cell lymphoma with poor prognosis. One hundred percent of PELs carry the genome of Kaposi sarcoma-associated herpesvirus and a majority are coinfected with Epstein-Barr virus (EBV). We profiled genomic aberrations in PEL cells using the Affymetrix 6.0 SNP array. This identified for the first time individual genes that are altered in PEL cells. Eleven of 13 samples (85%) were deleted for the fragile site tumor suppressors WWOX and FHIT. Alterations were also observed in the DERL1, ETV1, RASA4, TPK1, TRIM56, and VPS41 genes, which are yet to be characterized for their roles in cancer. Coinfection with EBV was associated with significantly fewer gross genomic aberrations, and PEL could be segregated into EBV-positive and EBV-negative clusters on the basis of host chromosome alterations. This suggests a model in which both host genetic aberrations and the 2 viruses contribute to the PEL phenotype.
authors.affiliation: Curriculum in Genetics and Molecular Biology, UNC Lineberger Comprehensive Cancer Center, UNC Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7290, USA.
authors.forename: Debasmita
authors.initials: D
authors.lastname: Roy
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Sin
authors.forename: Blossom
authors.initials: B
authors.lastname: Damania
authors.forename: Dirk P
authors.initials: DP
authors.lastname: Dittmer
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D005784:Gene Amplification; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D054685:Lymphoma, Primary Effusion / Q000235:genetics* / Q000821:virology; D009363:Neoplasm Proteins / Q000235:genetics*; D010088:Oxidoreductases / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000074584:WW Domain-Containing Oxidoreductase; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D010088:Oxidoreductases; D025521:Tumor Suppressor Proteins; D000074584:WW Domain-Containing Oxidoreductase; D000099170:Bis(5'-adenosyl)triphosphatase; C486071:WWOX protein, human