title: Mutational analysis of TP53, PTEN, PIK3CA and CTNNB1/beta-catenin genes in human herpesvirus 8-associated primary effusion lymphoma.
abstract: Human herpesvirus 8 (HHV-8)-associated primary effusion lymphoma is a rare non-Hodgkin's lymphoma often associated with Epstein-Barr virus (EBV) infection. Mutations in TP53, PTEN, PIK3CA, CTNNB1/beta-catenin genes and deletion of CDKN2A-ARF (p14(ARF)-p16(NK4a I) ) locus were investigated in sixteen primary primary effusion lymphoma tumors and seven primary effusion lymphoma cell lines using PCR and sequencing. TP53 mutations were detected in one primary primary effusion lymphoma tumor (6.2%) and two primary effusion lymphoma cell lines (28.6%). BC-3 and BCP-1 cell lines showed PTEN gene mutations, associated with a loss of PTEN protein expression in both cases. No mutations were detected in PIK3CA and CTNNB1/beta-catenin hotspot sequences. Only BC-3 contained a homozygous deletion of CDKN2A-ARF locus. Although detected at a higher frequency in primary effusion lymphoma cell lines than in primary primary effusion lymphoma tumors, TP53 and/or PTEN mutations, as well as deletion of CDKN2A-ARF locus are uncommon in primary effusion lymphoma, and are found to correlate with the EBV-negative status of primary effusion lymphoma tumors.
authors.affiliation: Department of Clinical Immunology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France. emmaboul@ioc.fiocruz.br
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Boulanger
authors.forename: Agnès
authors.initials: A
authors.lastname: Marchio
authors.forename: Saw-See
authors.initials: SS
authors.lastname: Hong
authors.forename: Pascal
authors.initials: P
authors.lastname: Pineau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D006566:Herpesviridae Infections / Q000150:complications / Q000235:genetics / Q000821:virology; D019288:Herpesvirus 8, Human; D006801:Humans; D054685:Lymphoma, Primary Effusion / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics*
chemical_list: C495270:CTNNB1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human