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

Clonal and subclonal TP53 molecular impairment is associated with prognosis and progression in multiple myeloma / Martello M.; Poletti A.; Borsi E.; Solli V.; Dozza L.; Barbato S.; Zamagni E.; Tacchetti P.; Pantani L.; Mancuso K.; Vigliotta I.; Rizzello I.; Rocchi S.; Armuzzi S.; Testoni N.; Marzocchi G.; Martinelli G.; Cavo M.; Terragna C.. - In: BLOOD CANCER JOURNAL. - ISSN 2044-5385. - STAMPA. - 12:1(2022), pp. 15.15-15.15. [10.1038/s41408-022-00610-y]

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

Martello M.;Poletti A.;Borsi E.;Solli V.;Barbato S.;Zamagni E.;Tacchetti P.;Pantani L.;Mancuso K.;Vigliotta I.;Rizzello I.;Rocchi S.;Armuzzi S.;Testoni N.;Marzocchi G.;Martinelli G.;Cavo M.;Terragna C.
2022

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 in use underestimate their incidence, hindering an optimal risk assessment and prognostication of MM patients. We have investigated the altered status of TP53 gene by SNPs array and sequencing techniques in a homogenous cohort of 143 newly diagnosed MM patients, evaluated both at diagnosis and at first relapse: single-hit on TP53 gene, either deletion or mutation, detected both at clonal and sub-clonal level, had a minor effect on outcomes. Conversely, the coexistence of both TP53 deletion and mutation, which defined the so-called double-hit patients, was associated with the worst clinical outcome (PFS: HR 3.34 [95% CI: 1.37–8.12] p = 0.008; OS: HR 3.47 [95% CI: 1.18–10.24] p = 0.02). Moreover, the analysis of longitudinal samples pointed out that TP53 allelic status might increase during the disease course. Notably, the acquisition of TP53 alterations at relapse dramatically worsened the clinical course of patients. Overall, our analyses showed these techniques to be highly sensitive to identify TP53 aberrations at sub-clonal level, emphasizing the poor prognosis associated with double-hit MM patients.
2022
Clonal and subclonal TP53 molecular impairment is associated with prognosis and progression in multiple myeloma / Martello M.; Poletti A.; Borsi E.; Solli V.; Dozza L.; Barbato S.; Zamagni E.; Tacchetti P.; Pantani L.; Mancuso K.; Vigliotta I.; Rizzello I.; Rocchi S.; Armuzzi S.; Testoni N.; Marzocchi G.; Martinelli G.; Cavo M.; Terragna C.. - In: BLOOD CANCER JOURNAL. - ISSN 2044-5385. - STAMPA. - 12:1(2022), pp. 15.15-15.15. [10.1038/s41408-022-00610-y]
Martello M.; Poletti A.; Borsi E.; Solli V.; Dozza L.; Barbato S.; Zamagni E.; Tacchetti P.; Pantani L.; Mancuso K.; Vigliotta I.; Rizzello I.; Rocchi S.; Armuzzi S.; Testoni N.; Marzocchi G.; Martinelli G.; Cavo M.; Terragna C.
File in questo prodotto:
File Dimensione Formato  
s41408-022-00610-y.pdf

accesso aperto

Tipo: Versione (PDF) editoriale
Licenza: Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY)
Dimensione 1.65 MB
Formato Adobe PDF
1.65 MB Adobe PDF Visualizza/Apri
41408_2022_610_MOESM1_ESM (1).docx

accesso aperto

Tipo: File Supplementare
Licenza: Licenza per Accesso Aperto. Altra tipologia di licenza compatibile con Open Access
Dimensione 1.7 MB
Formato Microsoft Word XML
1.7 MB Microsoft Word XML Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/880016
Citazioni
  • ???jsp.display-item.citation.pmc??? 10
  • Scopus 15
  • ???jsp.display-item.citation.isi??? 14
social impact