Evaluation of TP53 mutations with the AmpliChip p53 research test in chronic lymphocytic leukemia

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BlankEvaluation of TP53 mutations with the AmpliChip p53 research test in

chronic lymphocytic leukemia: Correlation with clinical outcome and gene

expression profiling.

S Chiaretti, S Tavolaro, M Marinelli, M Messina, I Del Giudice, FR Mauro, S

Santangelo, A Piciocchi, N Peragine, S Truong, N Patten, EM Ghia, I Torrente, MS

De Propris, M Nanni, J Lawrence, A Guarini, and R Foa

Genes Chromosomes Cancer, April 1, 2011; 50(4): 263-74.

Division of Hematology, Department of Cellular Biotechnologies and Hematology,

" Sapienza " University of Rome, Italy.

Given that TP53 alterations predict prognosis and response to therapy in chronic

lymphocytic leukemia (CLL), screening for TP53 mutations has an increasing role

in patient management. TP53 direct sequencing is a time-consuming method, while

the AmpliChip p53 Research Test is a novel non time-consuming microarray-based

resequencing assay and queries Exons 2-11. We evaluated the impact of TP53

mutations on clinical outcome by analyzing 98 untreated CLL using the AmpliChip

p53 Research Test and direct sequencing and performed microarrays analysis on

TP53 mutated and/or deleted cases. The AmpliChip p53 Research Test detected 17

mutations in 14 patients (17.3%); a significant association between TP53

mutations and del(17p) was recorded. From a clinical standpoint, a higher

percentage of mutation was found in CLL with unfavorable outcome (17.2% vs. 7.1%

in progressive vs. stable cases). Detection of TP53 mutations by the AmpliChip

p53 Research Test was associated with a significantly worse survival (P =

0.0002). Comparison of the array and direct sequencing tests showed that the p53

Research Test detected more mutations, although it failed to identify two

microdeletions. Finally, microarrays analysis showed a more distinctive

signature associated with del(17p) than with TP53 mutations, likely due to a

concomitant gene dosage effect. The AmpliChip p53 Research Test is a

straightforward method that bears prognostic value. This study confirms a high

percentage of TP53 mutations in CLL with unfavorable outcome and a significant

association between TP53 aberrations and del(17p). Finally, specific gene

expression profiles are recognized for TP53 alterations. ? 2011 Wiley-Liss, Inc.

PMID: 21319261