A possible role of the P53 gene deletion as a prognostic factor in multiple myeloma.
The role of P53 gene abnormalities in the pathogenesis of multiple myeloma (MM) and their potential use as prognostic indicators remain uncertain. To further define this question, we studied genomic DNA from 50 MM and one plasma cell leukemia patients by polymerase chain reaction single-strand conformation polymorphism and sequencing, and fluorescence in situ hybridization in order to detect P53 mutation and deletion, respectively. Kaplan-Meier survival curves and the log-rank test were used to analyze the survival data. No P53 mutation was detected in our patients. In contrast, P53 deletion, predominantly monoallelic, was detected in 8 of 51 (15.7%) patients. Similar frequencies of P53 deletion were observed in patients stratified by age ( P=0.71), gender ( P=0.44), status, and stage of the disease ( P=0.70 and P=0.23, respectively). However, patients with P53 deletion had significantly shorter median overall survival compared with those without a deletion (7.4 vs 139.0 months, P<0.0001). On univariate regression analysis, P53 deletion was a parameter for predicting shortened survival ( P=0.02). We concluded that P53 mutation may be seen as a prognostic indicator of limited value in MM. In contrast, P53 deletion may be seen as a prognostic indicator of poor outcome. However, as the cohort of patients is rather limited for a prognostic analysis, these results should be confirmed by further studies with larger sized samples.
Ortega
M M
MM
Department of Internal Medicine, State University of Campinas, Campinas, São Paulo, Brazil.
Melo
M B
MB
De Souza
C A
CA
Lorand-Metze
I
I
Costa
F F
FF
Lima
C S P
CS
D000328:Adult; D000367:Age Factors; D000368:Aged; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000235:genetics*; D015995:Prevalence; D011379:Prognosis; D012737:Sex Factors; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53