TY - JOUR
T1 - Activating PTPN11 mutations play a minor role in pediatric and adult solid tumors
AU - Martinelli, Simone
AU - Carta, Claudio
AU - Flex, Elisabetta
AU - Binni, Francesco
AU - Moretti, Sonia
AU - Puxeddu, Efisio
AU - Tonacchera, Massimo
AU - Pinchera, Aldo
AU - Mcdowell, Heather P.
AU - Dominici, Carlo
AU - Rosolen, Angelo
AU - Di Rocco, Concezio
AU - Riccardi, Riccardo
AU - Celli, Paolo
AU - Picardo, Mauro
AU - Genuardi, Maurizio
AU - Grammatico, Paola
AU - Sorcini, Mariella
AU - Tartaglia, Marco
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
KW - PTPN11 mutations
KW - solid tumors
KW - PTPN11 mutations
KW - solid tumors
UR - http://hdl.handle.net/10807/16301
U2 - 10.1016/j.cancergencyto.2005.10.003
DO - 10.1016/j.cancergencyto.2005.10.003
M3 - Article
SN - 0165-4608
VL - 166
SP - 124
EP - 129
JO - Cancer Genetics and Cytogenetics
JF - Cancer Genetics and Cytogenetics
ER -