p53 gene mutations in multiple myeloma

Centre for Haematological Oncology, General Infirmary at Leeds.
Molecular Pathology 03/1997; 50(1):18-20. DOI: 10.1136/mp.50.1.18
Source: PubMed


To assess whether p53 gene mutation is important in the pathogenesis and progression of multiple myeloma.
Thirty eight DNA samples (derived predominantly from bone marrow) obtained from 31 patients with multiple myeloma were examined for mutations in p53 exons 5-9 by polymerase chain reaction single strand conformation polymorphism. Twenty three samples were analysed at the time of diagnosis (one patient had plasma cell leukaemia), three in plateau phase, and 12 at relapse (one plasma cell leukaemia and one extramedullary relapse).
One p53 mutation was detected in this group of patients (3.2%). This was seen in the diagnostic bone marrow sample of a 35 year old man with stage IIA disease and occurred in exon 6 as a result of a silent A to G transition at codon 213 (CGA-->CGG), a polymorphism that has been reported in about 3% of breast and lung tumours.
p53 gene mutations are rare events in multiple myeloma and would seem to be of limited value as a prognostic factor.

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Available from: James ANTHONY Child, Feb 04, 2015
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    • "The correlation of mutations of p53 with detectable protein in lymphoid tumours is poor and therefore it seems preferable to restrict interpretation of data to studies were mutations have been measured. Studies of p53 in myeloma show a mutation rate of 2–4% (Preudhomme et al, 1992; Owen et al, 1997), although the frequency in end stage disease and in myeloma cell lines increases to 40%. This is reflected in studies of serial samples where p53 mutations identified in the terminal stage of disease were not found in samples from the plateau phase (Neri et al, 1993), suggesting a multi-step process with p53 mutation as a late event in tumour progression. "

    Preview · Article · Jan 1998 · British Journal of Haematology
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    Preview · Article · Dec 1997 · Molecular Pathology
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    ABSTRACT: In multiple myeloma (MM), previous studies showed that mutations of the p53 gene are rare events in patients with newly diagnosed disease, but it is not known whether deletions of p53 are of any significance in MM. To address this question, we used interphase fluorescence in situ hybridization (FISH) with a DNA probe specific for the p53 locus at 17p13 and investigated bone marrow plasma cells from 72 patients with MM (59 patients = 81.9% before therapy). By FISH, deletions of p53, which were found to be predominantly monoallelic, were detected in 32.8% and 54.5% of patients with newly diagnosed and relapsed MM, respectively. Karyotypes from six of the patients with a p53 deletion by FISH showed a structural abnormality of 17p in only one of them. Additional FISH studies including a distal-17p probe (specific for the D17S34 locus) provided evidence for an interstitial deletion on 17p resulting in loss of p53 hybridization signals in myeloma cells. Among all 59 patients with newly diagnosed MM, presence of a p53 deletion was associated with stage III (P = .054), but not with other laboratory and clinical parameters. Patients with a p53 deletion had significantly shorter survival time compared with those without a deletion, both from the time of diagnosis (median 13.9 v 38.7 months; P < .0001) and from the time of initiation of induction treatment consisting of conventional dose chemotherapy (median 15.9 months v median not reached at 38 months; P < .0002). On stepwise multivariate regression analysis, presence of a p53 deletion was the most significant independent parameter predicting for shortened survival (P = .002). We conclude that a p53 gene deletion, which can be identified by interphase FISH in almost a third of patients with newly diagnosed MM, is a novel prognostic factor predicting for short survival of MM patients treated with conventional-dose chemotherapy.
    No preview · Article · Aug 1998 · Blood
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