Activating PTPN11 mutations play a minor role in pediatric and adult solid tumors.
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.
Martinelli
Simone
S
Dipartimento di Biologia cellulare e Neuroscienze, Istituto Superiore di Sanità, Rome, Italy.
Carta
Claudio
C
Flex
Elisabetta
E
Binni
Francesco
F
Cordisco
Emanuela Lucci
EL
Moretti
Sonia
S
Puxeddu
Efisio
E
Tonacchera
Massimo
M
Pinchera
Aldo
A
McDowell
Heather P
HP
Dominici
Carlo
C
Rosolen
Angelo
A
Di Rocco
Concezio
C
Riccardi
Riccardo
R
Celli
Paolo
P
Picardo
Mauro
M
Genuardi
Maurizio
M
Grammatico
Paola
P
Sorcini
Mariella
M
Tartaglia
Marco
M
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
D047908:Intracellular Signaling Peptides and Proteins; D013912:Threonine; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases