title: Somatic PTPN11 mutations in childhood acute myeloid leukaemia.
abstract: Somatic mutations in PTPN11, the gene encoding the transducer SHP-2, have emerged as a novel class of lesions that upregulate RAS signalling and contribute to leukaemogenesis. In a recent study of 69 children and adolescents with de novo acute myeloid leukaemia (AML), we documented a non-random distribution of PTPN11 mutations among French-American-British (FAB) subtypes. Lesions were restricted to FAB-M5 cases, where they were relatively common (four of 12 cases). Here, we report on the results of a molecular screening performed on 181 additional unselected patients, enrolled in participating institutions of the Associazione Italiana Ematologia Oncologia Pediatrica-AML Study Group, to provide a more accurate picture of the prevalence, spectrum and distribution of PTPN11 mutations in childhood AML and to investigate their clinical relevance. We concluded that PTPN11 defects do not represent a frequent event in this heterogeneous group of malignancies (4.4%), although they recur in a considerable percentage of patients with FAB-M5 (18%). PTPN11 lesions rarely occur in other subtypes. Within the FAB-M5 group no clear association of PTPN11 mutations with any clinical variable was evident. Nearly two third of the patients with this subtype were found to harbour an activating mutation in PTPN11, NRAS, KRAS2 or FLT3.
authors.affiliation: Dipartimento di Biologia cellulare e Neuroscienze, Istituto Superiore di Sanità, 299-00161 Rome, Italy. mtartaglia@iss.it
authors.forename: Marco
authors.initials: M
authors.lastname: Tartaglia
authors.forename: Simone
authors.initials: S
authors.lastname: Martinelli
authors.forename: Ivano
authors.initials: I
authors.lastname: Iavarone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cazzaniga
authors.forename: Monica
authors.initials: M
authors.lastname: Spinelli
authors.forename: Emanuela
authors.initials: E
authors.lastname: Giarin
authors.forename: Valentina
authors.initials: V
authors.lastname: Petrangeli
authors.forename: Claudio
authors.initials: C
authors.lastname: Carta
authors.forename: Riccardo
authors.initials: R
authors.lastname: Masetti
authors.forename: Maurizio
authors.initials: M
authors.lastname: Aricò
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Mariella
authors.initials: M
authors.lastname: Sorcini
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins; D007948:Leukemia, Monocytic, Acute / Q000097:blood / Q000235:genetics; D007951:Leukemia, Myeloid / Q000097:blood / Q000235:genetics*; D007958:Leukocyte Count; D008297:Male; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D051941:fms-Like Tyrosine Kinase 3; D018631:ras Proteins
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C117307:KRAS protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins