title: A proportion of patients with lymphoma may harbor mutations of the perforin gene.
abstract: Perforin mutations have been demonstrated in a proportion of patients diagnosed with the familial form of hemophagocytic lymphohistiocytosis (HLH). In the present study, we evaluated whether some patients with lymphoma sharing clinical characteristics with HLH might harbor mutations of the perforin gene. We analyzed 29 patients and found that 4 patients, who developed either Hodgkin or non-Hodgkin lymphoma, had biallelic mutations of the perforin gene. One of these 4 patients, a 19-year-old female with T-cell lymphoma, had a brother carrying the same mutations who developed HLH. In 2 of the 4 patients with biallelic mutations of the perforin gene, we evaluated perforin expression by flow cytometry and natural killer (NK) activity and both were found to be absent. Moreover, we documented the presence of monoallelic mutations of the perforin gene in 4 more patients. One of these 4 latter patients also carried a mutation of the Fas gene. These data indicate that perforin deficiency, either alone or in combination with other mutations of genes involved in lymphocyte survival or functional activity, may be present in patients with lymphoma. These findings suggest that perforin also plays a key role in the mechanisms of immune surveillance that prevent tumor growth and/or development.
authors.affiliation: University of Pavia and Istituto di Ricovero e Cura a Carattere Scientifico, Policlinico San Matteo, Italy. rita.clementi@hsr.it
authors.forename: Rita
authors.initials: R
authors.lastname: Clementi
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Loïc
authors.initials: L
authors.lastname: Dupré
authors.forename: Alberto
authors.initials: A
authors.lastname: Garaventa
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Emmi
authors.forename: Marco
authors.initials: M
authors.lastname: Bregni
authors.forename: Graziella
authors.initials: G
authors.lastname: Cefalo
authors.forename: Antonia
authors.initials: A
authors.lastname: Moretta
authors.forename: Cesare
authors.initials: C
authors.lastname: Danesino
authors.forename: Margherita
authors.initials: M
authors.lastname: Comis
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
authors.forename: Ugo
authors.initials: U
authors.lastname: Ramenghi
authors.forename: Rita
authors.initials: R
authors.lastname: Maccario
authors.forename: Maurizio
authors.initials: M
authors.lastname: Aricò
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Roncarolo
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D007157:Immunologic Surveillance; D007694:Killer Cells, Natural / Q000276:immunology; D008223:Lymphoma / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D009154:Mutation; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor / Q000235:genetics
chemical_list: D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin