PTPN11

Overview

PTPN11 (SHP2) is a tyrosine phosphatase that acts upstream of RAS/MAPK signaling. In the corpus it is a rare RAS-pathway driver in histiocytosis.

Alterations observed in the corpus

  • Mutated in one histiocytosis patient in the Make-an-IMPACT rare-cancer cohort; patient was treated with a MEK inhibitor PMID:36862133.
  • Activating missense mutations in 2.9% (7/240) of high-risk neuroblastomas (nbl_broad_2013); all previously reported in COSMIC; one of only 5 statistically and biologically significant recurrently mutated genes in this low-mutation-burden pediatric tumor PMID:23334666
  • Activating mutations (e.g., p.Gly503Arg) found in near haploid ALL as part of RTK/Ras pathway alterations (71% of near haploid cases); one PTPN11 variant was inherited and Noonan syndrome-associated (all_stjude_2013, 124 pediatric cases) PMID:23334668
  • Part of the activated-signaling gene category in AML (alongside KIT, KRAS, NRAS, FLT3); contributes to the 59% signaling-pathway prevalence across 200 AML cases PMID:23634996
  • E69K and E76A activating mutations (previously described in juvenile myelomonocytic leukemia) exclusively co-occurring with FGFR1 mutations in pilocytic astrocytoma; PTPN11/SHP-2 expression globally elevated in this tumor type PMID:23817572
  • 2 expressed mutations detected in rhabdomyosarcoma, both restricted to fusion-negative (PFN) tumors; PTPN11 (SHP2) encodes an RAS-activating phosphatase PMID:24436047
  • Non-passenger mutation in breast adenoid cystic carcinoma (AdCC); rarely mutated in basal-like breast cancers. PMID:26095796
  • E76A/K hotspot in 2 desmoplastic melanoma tumors. PMID:26343386
  • Recurrent missense mutations in CLL (n=7, 1.3%); identified as a novel CLL driver modulating MYC activity in a 538-patient WES study PMID:26466571
  • PTPN11 co-occurs with NPM1 and modifies outcome in NPM1-mutated AML; part of the RTK-RAS pathway group identified in a 1540-patient AML genomic study PMID:27276561.
  • G503V mutation in AML (MEK-inhibitor target); D61Y co-mutation with SETBP1 D868N reclassified a 4-year-old’s diagnosis from de novo AML to JMML (which evolved into AML) in a pediatric precision-oncology cohort PMID:28007021

Cancer types (linked)

Co-occurrence and mutual exclusivity

  • None reported.

Therapeutic relevance

  • MEK inhibitor treatment reported for PTPN11-mutant histiocytosis patient in the direct-to-patient program PMID:36862133.

Open questions

  • None specific to PTPN11 in this cohort.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:23334666

This page was processed by crosslinker on 2026-05-14. - PMID:23334668

This page was processed by crosslinker on 2026-05-14. - PMID:23634996

This page was processed by crosslinker on 2026-05-14. - PMID:23817572

This page was processed by crosslinker on 2026-05-14. - PMID:24436047

This page was processed by crosslinker on 2026-05-14. - PMID:26095796

This page was processed by crosslinker on 2026-05-14. - PMID:26343386

This page was processed by crosslinker on 2026-05-14. - PMID:26466571

This page was processed by crosslinker on 2026-05-14. - PMID:27276561

This page was processed by entity-page-writer on 2026-05-15. - PMID:28007021

This page was processed by wiki-cli on 2026-05-14.