title: Molecular spectrum of TP53 mutations in plasma cell dyscrasias by next generation sequencing: an Italian cohort study and overview of the literature.
abstract: The prevalence of TP53 mutations greatly varies between tumor types; in multiple myeloma (MM) they were rarely detected at presentation, while increased frequency was reported with disease progression. Using next-generation sequencing, we analyzed TP53 exons 4-9 in a large representative cohort comprising patients with MM at diagnosis and more aggressive forms of plasma cell (PC) dyscrasia, identifying mutations in 4/129 (3%) MM, 6/24 (25%) primary PC leukemia, and 2/10 (20%) secondary PC leukemia cases. A similar increase in prevalence associated with disease aggressiveness (5%, 29.2% and 44%, respectively) was observed for TP53 deletion. Interestingly, in five patients mutations were not concomitant with TP53 deletion. Furthermore, longitudinal analysis revealed the acquisition of TP53 mutations in three of nineteen cases analyzed at relapse. Identified variants were mostly missense mutations concentrated in the DNA binding domain, only partly reflecting the pattern globally observed in human cancers. Our data confirm that TP53 mutations are rare in MM at presentation and rather represent a marker of progression, similarly to del(17p); however, their occurrence even in absence of deletions supports the importance of their assessment in patients with PC dyscrasia, in terms of both risk stratification and therapeutic implications.
authors: Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
authors: Marta
authors: M
authors: Lionetti
authors: Hematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors: Marzia
authors: M
authors: Barbieri
authors: Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
authors: Martina
authors: M
authors: Manzoni
authors: Hematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors: Sonia
authors: S
authors: Fabris
authors: Hematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors: Cecilia
authors: C
authors: Bandini
authors: Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy.
authors: Katia
authors: K
authors: Todoerti
authors: Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy.
authors: Filomena
authors: F
authors: Nozza
authors: Department of Translational Medicine, Division of Hematology, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
authors: Davide
authors: D
authors: Rossi
authors: Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy.
authors: Pellegrino
authors: P
authors: Musto
authors: Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.|Hematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors: Luca
authors: L
authors: Baldini
authors: Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.|Hematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors: Antonino
authors: A
authors: Neri
mesh_terms: D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D018450:Disease Progression; D005787:Gene Frequency; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007558:Italy; D009101:Multiple Myeloma / Q000235:genetics / Q000473:pathology; D009154:Mutation; D010265:Paraproteinemias / Q000235:genetics* / Q000473:pathology; D012196:Review Literature as Topic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53
keywords: TP53; multiple myeloma; mutational analysis; next-generation sequencing; plasma cell leukemia