title: Evaluation of TP53 mutations with the AmpliChip p53 research test in chronic lymphocytic leukemia: correlation with clinical outcome and gene expression profiling.
abstract: 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.
authors.affiliation: Division of Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Chiaretti
authors.forename: Simona
authors.initials: S
authors.lastname: Tavolaro
authors.forename: Marilisa
authors.initials: M
authors.lastname: Marinelli
authors.forename: Monica
authors.initials: M
authors.lastname: Messina
authors.forename: Ilaria
authors.initials: I
authors.lastname: Del Giudice
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Mauro
authors.forename: Simona
authors.initials: S
authors.lastname: Santangelo
authors.forename: Alfonso
authors.initials: A
authors.lastname: Piciocchi
authors.forename: Nadia
authors.initials: N
authors.lastname: Peragine
authors.forename: Sim
authors.initials: S
authors.lastname: Truong
authors.forename: Nancy
authors.initials: N
authors.lastname: Patten
authors.forename: Emanuela Maria
authors.initials: EM
authors.lastname: Ghia
authors.forename: Isabella
authors.initials: I
authors.lastname: Torrente
authors.forename: Maria Stefania
authors.initials: MS
authors.lastname: De Propris
authors.forename: Mauro
authors.initials: M
authors.lastname: Nanni
authors.forename: Jeff
authors.initials: J
authors.lastname: Lawrence
authors.forename: Anna
authors.initials: A
authors.lastname: Guarini
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002460:Cell Line; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D016158:Genes, p53 / Q000235:genetics*; D042822:Genomic Instability; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017354:Point Mutation; D011379:Prognosis; D017384:Sequence Deletion / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53