title: PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma.
abstract: Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that can present as a systemic or primary cutaneous disease. Systemic ALCL represents 2% to 5% of adult lymphoma but up to 30% of all pediatric cases. Two subtypes of systemic ALCL are currently recognized on the basis of the presence of a translocation involving the anaplastic lymphoma kinase ALK gene. Despite considerable progress, several questions remain open regarding the pathogenesis of both ALCL subtypes. To investigate the molecular pathogenesis and to assess the relationship between the ALK(+) and ALK(-) ALCL subtypes, we performed a genome-wide DNA profiling using high-density, single nucleotide polymorphism arrays on a series of 64 cases and 7 cell lines. The commonest lesions were losses at 17p13 and at 6q21, encompassing the TP53 and PRDM1 genes, respectively. The latter gene, coding for BLIMP1, was inactivated by multiple mechanisms, more frequently, but not exclusively, in ALK(-)ALCL. In vitro and in vivo experiments showed that that PRDM1 is a tumor suppressor gene in ALCL models, likely acting as an antiapoptotic agent. Losses of TP53 and/or PRDM1 were present in 52% of ALK(-)ALCL, and in 29% of all ALCL cases with a clinical implication.
authors.affiliation: Lymphoma and Genomics Research Program, IOR Institute of Oncology Research, Bellinzona, Switzerland;
authors.forename: Michela
authors.initials: M
authors.lastname: Boi
authors.forename: Andrea
authors.initials: A
authors.lastname: Rinaldi
authors.forename: Ivo
authors.initials: I
authors.lastname: Kwee
authors.forename: Paola
authors.initials: P
authors.lastname: Bonetti
authors.forename: Maria
authors.initials: M
authors.lastname: Todaro
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tabbò
authors.forename: Roberto
authors.initials: R
authors.lastname: Piva
authors.forename: Paola M V
authors.initials: PM
authors.lastname: Rancoita
authors.forename: András
authors.initials: A
authors.lastname: Matolcsy
authors.forename: Botond
authors.initials: B
authors.lastname: Timar
authors.forename: Thomas
authors.initials: T
authors.lastname: Tousseyn
authors.forename: Socorro Maria
authors.initials: SM
authors.lastname: Rodríguez-Pinilla
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Piris
authors.forename: Sílvia
authors.initials: S
authors.lastname: Beà
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Govind
authors.initials: G
authors.lastname: Bhagat
authors.forename: Steven H
authors.initials: SH
authors.lastname: Swerdlow
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Maurilio
authors.initials: M
authors.lastname: Ponzoni
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Piccaluga
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.forename: Stefano
authors.initials: S
authors.lastname: Pileri
authors.forename: Emanuele
authors.initials: E
authors.lastname: Zucca
authors.forename: Giorgio
authors.initials: G
authors.lastname: Inghirami
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertoni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000235:genetics*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008875:Middle Aged; D009368:Neoplasm Transplantation; D000074462:Positive Regulatory Domain I-Binding Factor 1; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D055815:Young Adult
chemical_list: D012097:Repressor Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1; C000626173:ALK protein, human; C000626174:Alk protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases