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.
| Original language | English |
|---|---|
| Pages (from-to) | 21353-61 |
| Number of pages | 9 |
| Journal | Oncotarget |
| Volume | 7 |
| Issue number | 16 |
| DOIs | |
| Publication status | Published - Apr 19 2016 |
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- Journal Article
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Molecular spectrum of TP53 mutations in plasma cell dyscrasias by next generation sequencing : an Italian cohort study and overview of the literature. / Lionetti, Marta; Barbieri, Marzia; Manzoni, Martina; Fabris, Sonia; Bandini, Cecilia; Todoerti, Katia; Nozza, Filomena; Rossi, Davide; Musto, Pellegrino; Baldini, Luca; Neri, Antonino.
In: Oncotarget, Vol. 7, No. 16, 19.04.2016, p. 21353-61.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Molecular spectrum of TP53 mutations in plasma cell dyscrasias by next generation sequencing
T2 - an Italian cohort study and overview of the literature
AU - Lionetti, Marta
AU - Barbieri, Marzia
AU - Manzoni, Martina
AU - Fabris, Sonia
AU - Bandini, Cecilia
AU - Todoerti, Katia
AU - Nozza, Filomena
AU - Rossi, Davide
AU - Musto, Pellegrino
AU - Baldini, Luca
AU - Neri, Antonino
PY - 2016/4/19
Y1 - 2016/4/19
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.18632/oncotarget.7241
DO - 10.18632/oncotarget.7241
M3 - Article
VL - 7
SP - 21353
EP - 21361
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 16
ER -