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Gene Symbol PTPN11
Synonyms BPTP3 | CFC | JMML | METCDS | NS1 | PTP-1D | PTP2C | SH-PTP2 | SH-PTP3 | SHP2
Gene Description PTPN11, protein tyrosine phosphatase non-receptor type 11, is a member of the PTP Src homology-2 (SH2) domain-containing phosphatases that induces the MAPK signal transduction pathway to regulate growth factor signaling and has been characterized as both an oncogene and tumor suppressor (PMID: 20337577, PMID: 28074573). PTPN11 activating mutations have been identified in a variety of tumors including, lung, colon, brain, thyroid, skin and heme (PMID: 18286234, PMID: 21407260), PTPN11 hypomethylation has been observed in gastric cancer (PMID: 32194661), and germline mutations are implicated in Noonan syndrome (PMID: 28328117, PMID: 32233106).

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 D835Y PTPN11 A72D hematologic cancer sensitive Crenolanib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib, in combination with Mekinist (trametinib), synergistically decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y and Ptpn11 A72D (PMID: 30651561). 30651561
FLT3 D835Y PTPN11 A72D hematologic cancer resistant Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib, did not decrease cell proliferation of transformed mouse cells expressing Flt3 D835Y and Ptpn11 A72D, indicating Ptpn11 A72D as a resistance mutation since Flt3 D835Y was sensitive alone (PMID: 30651561). 30651561
PTPN11 A72V myeloid leukemia resistant SHP099 Preclinical - Cell culture Actionable In a preclinical study, SHP099 had no effect on Erk1/2 phosphorylation, Bcl-xl expression, Parp cleavage, and growth of myeloid cells expressing PTPN11 A72V in culture (PMID: 29568093). 29568093
PTPN11 act mut lung non-small cell carcinoma sensitive Refametinib Preclinical Actionable In a preclinical study, Refemetinib (BAY86-9766) inhibited growth of NSCLC cells harboring activating PTPN11 mutations in culture (J Clin Oncol 33, 2015(Suppl; abstr 11077)). detail...
PTPN11 D61Y myeloid leukemia resistant SHP099 Preclinical - Cell culture Actionable In a preclinical study, SHP099 had no effect on Erk1/2 phosphorylation, Bcl-xl expression, Parp cleavage, and growth of myeloid cells expressing PTPN11 D61Y in culture (PMID: 29568093). 29568093
PTPN11 dec exp myeloid leukemia resistant SHP099 Preclinical - Cell culture Actionable In a preclinical study, SHP099 had no effect on Erk1/2 phosphorylation, Bcl-xl expression, Parp cleavage, and growth of PTPN11 knock-out myeloid cells in culture (PMID: 29568093). 29568093
BRAF mut PTPN11 dec exp colorectal cancer sensitive PLX4720 Preclinical - Cell culture Actionable In a preclinical study, knocking down of Ptpn11 expression via shRNA sensitized BRAF mutant colorectal cancer cell lines to PLX4720 in culture (PMID: 26351322). 26351322
PTPN11 E69K myeloid leukemia sensitive SHP099 Preclinical - Cell culture Actionable In a preclinical study, SHP099 inhibited Erk1/2 phosphorylation, Bcl-xl expression, Parp cleavage, and growth of myeloid cells expressing PTPN11 A72V in culture (PMID: 29568093). 29568093
PTPN11 E76K leukemia sensitive U0126 Preclinical Actionable In a preclinical study, U0126 induced apoptotic activity of leukemia cells expressing PTPN11 E76K in culture (PMID: 17942397). 17942397
PTPN11 E76K leukemia sensitive PD98059 Preclinical Actionable In a preclinical study, PD98059 induced apoptotic activity of leukemia cells expressing PTPN11 E76K in culture (PMID: 17942397). 17942397
PTPN11 E76K juvenile myelomonocytic leukemia sensitive Cryptotanshinone Preclinical Actionable In a preclinical study, myeloid cells harboring PTPN11 E76K were sensitive to cryptotanshinone in culture, resulting in decreased cell growth (PMID: 23957426). 23957426
PTPN11 E76K hematologic cancer sensitive II-B08 Preclinical Actionable In a preclinical study, hematopoietic progenitor cells expressing PTPN11 E76K were sensitive to II-B08, resulting in decreased cell proliferation (PMID: 20170098). 20170098
PTPN11 E76K myeloid leukemia resistant SHP099 Preclinical - Cell culture Actionable In a preclinical study, SHP099 had no effect on Erk1/2 phosphorylation, Bcl-xl expression, Parp cleavage, and growth of myeloid cells expressing PTPN11 E76K in culture (PMID: 29568093). 29568093
BRAF G596R PTPN11 E76K colorectal cancer resistant RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, expression of PTPN11 E76K in colorectal cancer cells harboring BRAF G596R abolished their sensitivity to RMC-4550-induced inhibition of Erk phosphorylation and proliferation in culture (PMID: 30104724). 30104724
PTPN11 mutant juvenile myelomonocytic leukemia not applicable N/A Clinical Study Emerging In two clinical studies, PTPN11 mutations were frequently identified in patients with juvenile myelomonocytic leukemia and were found to be associated with poor survival (PMID: 19047918, PMID: 21901340), suggesting that this may serve as a future prognostic biomarker. 21901340 19047918
IDH1 wild-type PTPN11 mut glioblastoma multiforme predicted - sensitive Pembrolizumab Clinical Study - Cohort Actionable In a retrospective analysis, MAPK pathway mutations were significantly enriched in patients with IDH1 wild-type glioblastoma who responded to anti-PD-1 therapy with either Keytruda (pembrolizumab) or Opdivo (nivolumab), compared to those who did not respond (odds ratio=12.8, p=0.019), with 4 MAPK pathway mutations (2 in BRAF, 2 in PTPN11) identified in 13 responders and 1 (BRAF) in 32 non-responders (PMID: 30742119). 30742119
IDH1 wild-type PTPN11 mut glioblastoma multiforme predicted - sensitive Nivolumab Clinical Study - Cohort Actionable In a retrospective analysis, MAPK pathway mutations were significantly enriched in patients with IDH1 wild-type glioblastoma who responded to anti-PD-1 therapy with either Keytruda (pembrolizumab) or Opdivo (nivolumab), compared to those who did not respond (odds ratio=12.8, p=0.019), with 4 MAPK pathway mutations (2 in BRAF, 2 in PTPN11) identified in 13 responders and 1 (BRAF) in 32 non-responders (PMID: 30742119). 30742119
PTPN11 T253M PTPN11 Q257L lung non-small cell carcinoma resistant Selumetinib + SHP099 Preclinical - Cell culture Actionable In a preclinical study, pancreatic ductal adenocarcinoma cells co-expressing PTPN11 T253M and PTPN11 Q257L were resistant to the combination therapy, Selumetinib (AZD6244) and SHP099, in culture (PMID: 30045908). 30045908