PTPN11 encodes SHP2, a member of the non-receptor protein tyrosine phosphatase (PTP) family that regulates growth factor and cytokine signaling and plays a key role in the proliferation and survival of hematopoietic cells. PTPN11 mutation is directly associated with the pathogenesis of Noonan syndrome and childhood leukemias. Despite its direct function in protein dephosphorylation, SHP2 plays an overall positive role in transducing signals. Germline and somatic mutations that result in increased activity of PTPN11 have been described in Noonan's syndrome (approximately 50%), juvenile myelomonocytic leukemia (35-42%), pediatric and adult myelodysplasic syndromes (4-10%), B cell acute lymphoblastic leukemia (5-10%), as well as pediatric and adult acute myeloid leukemia (5-10%). These gain of function mutations most often occur as heterozygous missense mutations located in exon 3 (SH2 domain) or exon 13 (phosphatase domain) . Within cases of juvenile myelomonocytic leukemia, mutations of PTPN11 tend to be exclusive of mutations in RAS, CBL and NF-1. PTPN11 mutations in adult AML are associated with a normal karyotype and concurrent NPM1 mutation, but no alteration of the FLT3. In one study, myelodysplastic syndromes with PTPN11 mutations were shown to have a worse overall survival. Small molecule inhibitors of PTPN11 are currently being developed.

The PTPN11gene encodes SHP-2, a widely expressed cytoplasmic protein tyrosine phosphatase. SHP-2 is essential for activation of the RAS/MAPK signaling cascade. Most mutations are gain-of-function and result in prolonged ligand-dependent activation of the RAS/MAPK cascade. Germ-line PTPN11 mutations cause Noonan syndrome, a developmental disorder characterized by an increased risk of malignancies. Activating somatic mutations in PTPN11 have been documented in certain hematologic malignancies but they are infrequent in solid tumors. According to TCGA data base, about 2% of all the glial tumors harbor somatic mutations in PTPN11 gene but their prognostic and therapeutic significance remains to be fully elucidated. The utility of SHP2 inhibitors continues to be explored in some preclinical studies.

The PTPN11gene encodes SHP-2, a widely expressed cytoplasmic protein tyrosine phosphatase. SHP-2 is essential for activation of the RAS/MAPK signaling cascade. Most mutations are gain-of-function and result in prolonged ligand-dependent activation of the RAS/MAPK cascade. Germ-line PTPN11 mutations cause Noonan syndrome, a developmental disorder characterized by an increased risk of malignancies. Activating somatic mutations in PTPN11 have been documented in certain hematologic malignancies but they are infrequent in solid tumors. About 3% of all lung cancers harbor somatic mutations in PTPN11 gene but their prognostic and therapeutic significance remains to be fully elucidated. The utility of SHP2 inhibitors continues to be explored in some preclinical studies.

This gene is a known cancer gene.

This gene is a known cancer gene.

The PTPN11gene encodes SHP-2, a widely expressed cytoplasmic protein tyrosine phosphatase. SHP-2 is essential for activation of the RAS/MAPK signaling cascade. Most mutations are gain-of-function and result in prolonged ligand-dependent activation of the RAS/MAPK cascade. Germ-line PTPN11 mutations cause Noonan syndrome, a developmental disorder characterized by an increased risk of malignancies. Activating somatic mutations in PTPN11 have been documented in certain hematologic malignancies but they are infrequent in solid tumors. About 3% of all lung cancers harbor somatic mutations in PTPN11 gene but their prognostic and therapeutic significance remains to be fully elucidated. The PTPN11 V497L variant identified in this case has not been characterized in the literature and therefore its effect on protein function is unknown. This variant is best classified as a variant of uncertain significance. The utility of SHP2 inhibitors continues to be explored in some preclinical studies.

The PTPN11gene encodes SHP-2, a widely expressed cytoplasmic protein tyrosine phosphatase. SHP-2 is essential for activation of the RAS/MAPK signaling cascade. Most mutations are gain-of-function and result in prolonged ligand-dependent activation of the RAS/MAPK cascade. Germ-line PTPN11 mutations cause Noonan syndrome, a developmental disorder characterized by an increased risk of malignancies. Activating somatic mutations in PTPN11 have been documented in certain hematologic malignancies but they are infrequent in solid tumors. The G503V variant results in increased phosphatase activity compared to the wild-type protein in culture. About 3% of all lung cancers harbor somatic mutations in PTPN11 gene but their prognostic and therapeutic significance remains to be fully elucidated. The utility of SHP2 inhibitors continues to be explored in some preclinical studies.

The PTPN11gene encodes SHP-2, a widely expressed cytoplasmic protein tyrosine phosphatase. SHP-2 is essential for activation of the RAS/MAPK signaling cascade. Most mutations are gain-of-function and result in prolonged ligand-dependent activation of the RAS/MAPK cascade. Germ-line PTPN11 mutations cause Noonan syndrome, a developmental disorder characterized by an increased risk of malignancies. Activating somatic mutations in PTPN11 have been documented in certain hematologic malignancies but they are infrequent in solid tumors. Approximately 2% of colonic adenocarcinomas harbor somatic mutations in the PTPN11 gene. The E76K variant of PTPN11 has been found to be oncogenic in gliomas, but their prognostic and therapeutic significance in colonic adenocarcinomas remains to be fully elucidated (https://oncokb.org/#/gene/PTPN11/alteration/E76K).