title: Genome-wide DNA profiling better defines the prognosis of chronic lymphocytic leukaemia.
abstract: The integration of molecular and clinical information to tailor treatments remains an important research challenge in chronic lymphocytic leukaemia (CLL). This study aimed to identify genomic lesions associated with a poor outcome and a higher risk of histological transformation. A mono-institutional cohort of 147 cases was used as the test series, and a multi-institutional cohort of 176 cases as a validation series. Genomic profiles were obtained using Affymetrix SNP 6.0. The impact of the recurrent minimal common regions (MCRs) on overall survival was evaluated by univariate analysis followed by multiple-test correction. The independent prognostic significance was assessed by multivariate analysis. Eight MCRs showed a prognostic impact: gains at 2p25.3-p22.3 (MYCN), 2p22.3, 2p16.2-p14 (REL), 8q23.3-q24.3 (MYC), losses at 8p23.1-p21.2, 8p21.2, and of the TP53 locus. Gains at 2p and 8q and TP53 inactivation maintained prognostic significance in multivariate analysis and a hierarchical model confirmed their relevance. Gains at 2p also determined a higher risk of Richter syndrome transformation. The prediction of outcome for CLL patients might be improved by evaluating the presence of gains at 2p and 8q as novel genomic regions besides those included in the 'standard' fluorescence in situ hybridization panel.
authors.affiliation: Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland Division of Haematology, Azienda Ospedaliera S. Maurizio, Bolzano/Bozen, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rinaldi
authors.forename: Michael
authors.initials: M
authors.lastname: Mian
authors.forename: Ivo
authors.initials: I
authors.lastname: Kwee
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.forename: Clara
authors.initials: C
authors.lastname: Deambrogi
authors.forename: Afua A
authors.initials: AA
authors.lastname: Mensah
authors.forename: Francesco
authors.initials: F
authors.lastname: Forconi
authors.forename: Valeria
authors.initials: V
authors.lastname: Spina
authors.forename: Emanuele
authors.initials: E
authors.lastname: Cencini
authors.forename: Daniela
authors.initials: D
authors.lastname: Drandi
authors.forename: Marco
authors.initials: M
authors.lastname: Ladetto
authors.forename: Rita
authors.initials: R
authors.lastname: Santachiara
authors.forename: Roberto
authors.initials: R
authors.lastname: Marasca
authors.forename: Valter
authors.initials: V
authors.lastname: Gattei
authors.forename: Franco
authors.initials: F
authors.lastname: Cavalli
authors.forename: Emanuele
authors.initials: E
authors.lastname: Zucca
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertoni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055028:Comparative Genomic Hybridization; D016172:DNA Fingerprinting; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016571:Neural Networks, Computer; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult