Clonal and subclonal TP53 molecular impairment is associated with prognosis and progression in multiple myeloma

• DOI: 10.1038/s41408-022-00610-y
• Publication Date: 2022-01-26T08:02:54Z
• Authors: M. Martello; A. Poletti; E. Borsi; V. Solli; L. Dozza; S. Barbato; E. Zamagni; P. Tacchetti; L. Pantani; K. Mancuso; I. Vigliotta; I. Rizzello; S. Rocchi; S. Armuzzi; N. Testoni; G. Marzocchi; G. Martinelli; M. Cavo; C. Terragna
• Keywords: Male; 0303 health sciences; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Middle Aged; Prognosis; Polymorphism, Single Nucleotide; Article; 03 medical and health sciences; Aged; Chromosome Deletion; Disease Progression; Female; Humans; Male; Middle Aged; Multiple Myeloma; Mutation; Neoplasm Recurrence, Local; Prognosis; Tumor Suppressor Protein p53; Polymorphism, Single Nucleotide; Mutation; Disease Progression; Humans; Female; Chromosome Deletion; Neoplasm Recurrence, Local; Tumor Suppressor Protein p53; Multiple Myeloma; RC254-282; Aged

Abstract Aberrations on TP53 , either as deletions of chromosome 17p (del17p) or mutations, are associated with poor outcome in multiple myeloma (MM), but conventional detection methods currently use underestimate their incidence, hindering an optimal risk assessment and prognostication MM patients. We have investigated the altered status gene by SNPs array sequencing techniques a homogenous cohort 143 newly diagnosed patients, evaluated both at diagnosis first relapse: single-hit gene, deletion mutation, detected clonal sub-clonal level, had minor effect outcomes. Conversely, coexistence which defined so-called double-hit was worst clinical (PFS: HR 3.34 [95% CI: 1.37–8.12] p = 0.008; OS: 3.47 1.18–10.24] 0.02). Moreover, analysis longitudinal samples pointed out that allelic might increase during disease course. Notably, acquisition alterations relapse dramatically worsened course Overall, our analyses showed these to be highly sensitive identify aberrations emphasizing prognosis