title: Two novel methods for rapid detection and quantification of DNMT3A R882 mutations in acute myeloid leukemia.
abstract: DNMT3A mutations represent one of the most frequent gene alterations detectable in acute myeloid leukemia with normal karyotype. Although various recurrent somatic mutations of DNMT3A have been described, the most common mutation is located at amino acid R882 in the methyltransferase domain of the gene. DNMT3A mutations have been reported to be stable during disease progression and are associated with unfavorable outcome in acute myeloid leukemia patients with normal karyotype. Because of their prognostic significance and high stability during disease evolution, DNMT3A mutations might represent highly informative biomarkers for minimal residual disease monitoring. We describe a new rapid diagnostic RT-PCR assay based on TauI restriction enzyme reaction to identify DNMT3A R882 mutations at diagnosis. In addition, we developed a sensitive and specific test based on peptide nucleic acid real-time PCR technology to monitor DNMT3A R882H mutation. We identified 24 DNMT3A R882H mutated patients out of 134 acute myeloid leukemia screened samples and we analyzed in these patients the kinetics of minimal residual disease after induction and consolidation therapy. This assay may be useful to better assess response to therapy in patients with acute myeloid leukemia bearing the DNMT3A R882H mutation.
authors.affiliation: Department of Biomedicine and Prevention, The University Tor Vergata, Rome, Italy; Neuro-Oncohematology Unit, The Santa Lucia Foundation, Rome, Italy.
authors.forename: Melissa
authors.initials: M
authors.lastname: Mancini
authors.affiliation: Department of Medical Oncology ACTREC, Tata Memorial Centre Navi Mumbai, India.
authors.forename: Syed Khizer
authors.initials: SK
authors.lastname: Hasan
authors.affiliation: Department of Biomedicine and Prevention, The University Tor Vergata, Rome, Italy; Neuro-Oncohematology Unit, The Santa Lucia Foundation, Rome, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Ottone
authors.affiliation: Department of Biomedicine and Prevention, The University Tor Vergata, Rome, Italy; Neuro-Oncohematology Unit, The Santa Lucia Foundation, Rome, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Lavorgna
authors.affiliation: Department of Biomedicine and Prevention, The University Tor Vergata, Rome, Italy; Neuro-Oncohematology Unit, The Santa Lucia Foundation, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ciardi
authors.affiliation: Neuroimmunology and Flow Cytometry Units, The Santa Lucia Foundation-I.R.C.C.S., Rome, Italy.
authors.forename: Daniela F
authors.initials: DF
authors.lastname: Angelini
authors.affiliation: Department of Biomedicine and Prevention, The University Tor Vergata, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Agostini
authors.affiliation: Department of Biomedicine and Prevention, The University Tor Vergata, Rome, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Venditti
authors.affiliation: Department of Biomedicine and Prevention, The University Tor Vergata, Rome, Italy; Neuro-Oncohematology Unit, The Santa Lucia Foundation, Rome, Italy. Electronic address: francesco.lo.coco@uniroma2.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo-Coco
mesh_terms: D000293:Adolescent; D000328:Adult; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: C000717967:DNMT3A protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A