title: Incidence of 17p deletions and TP53 mutation in myelodysplastic syndrome and acute myeloid leukemia with 5q deletion.
abstract: TP53 mutations are frequent in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with complex karyotype that include del(5q) and are often associated with deletion of 17p. They have also recently been observed in MDS with isolated del(5q). We assessed the incidence of 17p deletion detected by fluorescence in situ hybridization (FISH) and of TP53 mutations detected by direct sequencing and their correlation and prognostic value in 26 MDS and 17 AML with del(5q). In the 20 cases with isolated del(5q) or one additional abnormality, no 17p deletion was found and 3 of the 18 cases analyzed (17%) had TP53 mutation. In the 23 patients with complex karyotype, 17p deletion was suspected by conventional cytogenetics in 15 cases and confirmed by FISH in 10 of them, while TP53 mutation was found in 8 of the 15 patients tested (53%), only five of whom had 17p deletion. In the whole patient series, TP53 mutations were associated with shorter survival (P = 0.07). We confirm the existence of TP53 mutations in 17% of MDS with isolated del(5q). In patients with del(5q) and complex karyotype, FISH and direct sequencing are complementary techniques to analyze TP53 abnormalities. Our findings also suggest that sequencing of the TP53 gene should be included in the study of patients with del(5q) as a single abnormality or in complex karyotype before lenalidomide treatment.
authors.affiliation: Laboratoire d'Hématologie, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris (AP-HP)/Université Paris 13, Bobigny. France.
authors.forename: Amel
authors.initials: A
authors.lastname: Sebaa
authors.forename: Lionel
authors.initials: L
authors.lastname: Ades
authors.forename: Fanny
authors.initials: F
authors.lastname: Baran-Marzack
authors.forename: Marie-Joelle
authors.initials: MJ
authors.lastname: Mozziconacci
authors.forename: Dominique
authors.initials: D
authors.lastname: Penther
authors.forename: Sophie
authors.initials: S
authors.lastname: Dobbelstein
authors.forename: Aspasia
authors.initials: A
authors.lastname: Stamatoullas
authors.forename: Christian
authors.initials: C
authors.lastname: Récher
authors.forename: Thomas
authors.initials: T
authors.lastname: Prebet
authors.forename: Soraya
authors.initials: S
authors.lastname: Moulessehoul
authors.forename: Pierre
authors.initials: P
authors.lastname: Fenaux
authors.forename: Virginie
authors.initials: V
authors.lastname: Eclache
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53