title: Activating PTPN11 mutations play a minor role in pediatric and adult solid tumors.
abstract: The PTPN11 gene encodes SHP-2, a widely expressed cytoplasmic protein tyrosine phosphatase functioning as a signaling transducer. Germ-line PTPN11 mutations cause Noonan syndrome (NS), a developmental disorder characterized by an increased risk of malignancies. Recently, a novel class of activating mutations in PTPN11 has been documented as a somatic event in a heterogeneous group of leukemias. Because of the relatively higher prevalence of certain solid tumors in children with NS and the positive modulatory function of SHP-2 in RAS signaling, a wider role for activating PTPN11 mutations in cancer has been hypothesized. Here, we screened a number of solid tumors, including those documented in NS or in which deregulated RAS signaling occurs at significant frequency, for PTPN11 mutations. No disease-associated mutation was identified in rhabdomyosarcoma (n = 13), neuroblastoma (n = 32), melanoma (n = 50), thyroid (n = 85), and colon (n = 48) tumors; a novel missense change, promoting an increased basal phosphatase activity of SHP-2, was observed in one glioma specimen. Our data document that deregulated SHP-2 function does not represent a major molecular event in pediatric and adult tumors, further supporting our previous evidence indicating that the oncogenic role of PTPN11 mutations is cell-context specific.
authors.affiliation: Dipartimento di Biologia cellulare e Neuroscienze, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Martinelli
authors.forename: Claudio
authors.initials: C
authors.lastname: Carta
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Flex
authors.forename: Francesco
authors.initials: F
authors.lastname: Binni
authors.forename: Emanuela Lucci
authors.initials: EL
authors.lastname: Cordisco
authors.forename: Sonia
authors.initials: S
authors.lastname: Moretti
authors.forename: Efisio
authors.initials: E
authors.lastname: Puxeddu
authors.forename: Massimo
authors.initials: M
authors.lastname: Tonacchera
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinchera
authors.forename: Heather P
authors.initials: HP
authors.lastname: McDowell
authors.forename: Carlo
authors.initials: C
authors.lastname: Dominici
authors.forename: Angelo
authors.initials: A
authors.lastname: Rosolen
authors.forename: Concezio
authors.initials: C
authors.lastname: Di Rocco
authors.forename: Riccardo
authors.initials: R
authors.lastname: Riccardi
authors.forename: Paolo
authors.initials: P
authors.lastname: Celli
authors.forename: Mauro
authors.initials: M
authors.lastname: Picardo
authors.forename: Maurizio
authors.initials: M
authors.lastname: Genuardi
authors.forename: Paola
authors.initials: P
authors.lastname: Grammatico
authors.forename: Mariella
authors.initials: M
authors.lastname: Sorcini
authors.forename: Marco
authors.initials: M
authors.lastname: Tartaglia
mesh_terms: D000328:Adult; D002648:Child; D015331:Cohort Studies; D004789:Enzyme Activation; D005091:Exons / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D013912:Threonine / Q000737:chemistry
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D013912:Threonine; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases