Mutations in TP53 are exclusively associated with del(17p) in multiple myeloma

Abstract

Deletion of the 17p13 chromosomal region [del(17p)] is associated with a poor outcome in multiple myeloma. Most of the studies have targeted the TP53 gene for deletion analyses, although no study showed that this gene is the deletion target. In order to address this issue, we sequenced the TP53 gene in 92 patients with multiple myeloma at diagnosis, 54 with a del(17p) and 38 lacking del(17p). At least one mutation was found in 20 patients, all of them presenting a del(17p). The analysis of the mutation location showed that virtually all of them occurred in highly conserved domains involved in the DNA-protein interactions. In conclusion, we showed that 37% of the myeloma patients with del(17p) present a TP53 mutation versus 0% in patients lacking the del(17p). The prognostic significance of these mutations remains to be evaluated.

Validation of multiple myeloma risk stratification indices in routine clinical practice: Analysis of data from the Czech Myeloma Group Registry of Monoclonal Gammopathies

“…The interpretation and different cutoffs used might produce a bias in our results. Mutations in TP53 domain are tightly bound to del(17p) in MM as showed by Lodé et al 23. They demonstrated that 0% of MM patients without del(17p) presented with a mutation in TP53; conversely, not all (ie, only 37%) of patients with del(17p) exhibited a TP53 mutation.…”

Restoration of microRNA-214 expression reduces growth of myeloma cells through positive regulation of P53 and inhibition of DNA replication

“…35 Mutations of P53 are relatively rare in newly diagnosed MM, occurring in approximately 5% of patients, although the frequency of mutations appears to increase with advancing disease. 36,37 On the other hand, deletion (mainly mono-allelic) of P53 occurs in about 10% of MM cases. 36,38 In spite of this rather low incidence, p53 may play a broader role in myeloma pathogenesis than previously thought, since an imbalance in p53 with biological consequences in myeloma cells can also be induced through post-transcriptional mechanisms.…”

Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenstrom's macroglobulinemia

“…27 In MM, 63% of 17p deletions were not associated with TP53 mutation. 28 Few data on TP53 mutations in WM have been reported. The recently established WM cell line MWCL-1 is reported to carry a monoallelic 17p deletion and a missense mutation in exon 5 of the remaining copy of TP53, both anomalies being present in the original patient's biopsy.…”