title: Molecular features of primary mediastinal B-cell lymphoma: involvement of p16INK4A, p53 and c-myc.
abstract: Primary mediastinal B-cell lymphoma (PMBL) shows chromosome 9p anomalies in 50% of cases. Based on reports that p16INK4A gene, located on this chromosomal arm, is frequently altered in aggressive lymphomas, we analysed for alterations of this gene in 27 cases of PMBL, which were part of a series of 32 PMBL cases that have been characterized for alterations in c-myc, p53, N-ras, bcl-1, bcl-2, bcl-6 and for Epstein-Barr virus (EBV) infection. Four cases showed p16INK4A gene anomalies, including three with promoter methylation and one homozygous deletion. Eight PMBLs showed c-myc rearrangements. Three additional cases showed sequence variations in the c-myc P2 promoter, two of which consisted of the same germline variation involving a novel polymorphic XhoI site. Four tumours contained p53 gene mutations and three had clonal EBV infection. One case had a bcl-6 rearrangement. In conclusion, our study shows that p16INK4, c-myc and p53 alterations occur in 15%, 25% and 13% of PMBLs, respectively. EBV monoclonality was found in 9% of cases, whereas no abnormality was detected in bcl-1, bcl-2 and N-ras. Thus, none of the common genetic aberrations seen in other types of non-Hodgkin's lymphomas appears to be stringently involved in the pathogenesis of this unique lymphoma type.
authors.affiliation: Dipartimento di Patologia, Sezione Anatomia Patologica, Università di Verona, Italy. scarpa@anpat.univr.it
authors.forename: A
authors.initials: A
authors.lastname: Scarpa
authors.forename: P S
authors.initials: PS
authors.lastname: Moore
authors.forename: G
authors.initials: G
authors.lastname: Rigaud
authors.forename: G
authors.initials: G
authors.lastname: Inghirami
authors.forename: M
authors.initials: M
authors.lastname: Montresor
authors.forename: M
authors.initials: M
authors.lastname: Menegazzi
authors.forename: G
authors.initials: G
authors.lastname: Todeschini
authors.forename: F
authors.initials: F
authors.lastname: Menestrina
mesh_terms: D000328:Adult; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D017353:Gene Deletion; D016259:Genes, myc / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics*; D008297:Male; D008479:Mediastinal Neoplasms / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D025521:Tumor Suppressor Proteins
chemical_list: C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025521:Tumor Suppressor Proteins