Research Papers:

Molecular spectrum of TP53 mutations in plasma cell dyscrasias by next generation sequencing: an Italian cohort study and overview of the literature

Marta Lionetti _, Marzia Barbieri, Martina Manzoni, Sonia Fabris, Cecilia Bandini, Katia Todoerti, Filomena Nozza, Davide Rossi, Pellegrino Musto, Luca Baldini and Antonino Neri

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Oncotarget. 2016; 7:21353-21361. https://doi.org/10.18632/oncotarget.7241

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Marta Lionetti1, Marzia Barbieri2, Martina Manzoni1, Sonia Fabris2, Cecilia Bandini2, Katia Todoerti3, Filomena Nozza3, Davide Rossi4, Pellegrino Musto3, Luca Baldini1,2, Antonino Neri1,2

1Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy

2Hematology Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy

3Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture (PZ), Italy

4Department of Translational Medicine, Division of Hematology, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy

Correspondence to:

Antonino Neri, e-mail: [email protected]

Marta Lionetti, e-mail: [email protected]

Keywords: multiple myeloma, plasma cell leukemia, TP53, next-generation sequencing, mutational analysis

Received: October 9, 2015    Accepted: January 19, 2016    Published: February 08, 2016


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.

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