|Transcript ID (GRCh37/hg19)||ENST00000351677|
|Tumor Type||Primary Site|
This gene is a known cancer gene.
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.