SMO

Overview

SMO (Smoothened) is a transmembrane protein in the Hedgehog signaling pathway. In the corpus, SMO point mutations are exclusive to the MG2 (NF2-wildtype, benign) molecular group of meningiomas.

Alterations observed in the corpus

  • SMO point mutations were identified in a copy-number-neutral subset of MG2 meningiomas (NF2-wildtype, benign); SMO mutations are exclusive to MG2 and mutually exclusive with NF2 mutations PMID:34433969.
  • Recurrently mutated in medulloblastoma WGS/WES cohort (76 tumors, ICGC); SMO activating mutations identified predominantly in the SHH-subgroup of medulloblastoma PMID:22832583
  • Target of saridegib (IPI-926); preclinical mouse data showed gemcitabine + saridegib extended survival in pancreatic cancer, but the parallel human phase II trial was halted after interim analysis showed inferior survival; long-term continuous Smoothened targeting was found to induce a more aggressive phenotype in early-stage disease PMID:23999436
  • Hedgehog-pathway alteration observed in pancreatic ductal adenocarcinoma (along with GLI2, GLI3, PTCH1, LRP2). PMID:25855536
  • Different mutations seen pre- and post-therapy in one medulloblastoma patient, evidence of convergent evolution at recurrence PMID:26760213
  • Mutated in a subset of SHH medulloblastomas in the 491-sample ICGC cohort PMID:28726821

Cancer types (linked)

  • MNG — point mutations exclusive to the MG2 (NF2-wildtype) molecular group; part of the TRAF7/AKT1/KLF4/SMO driver set PMID:34433969.

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • MG2 tumors harboring SMO mutations may be amenable to Hedgehog pathway inhibitors; MG2 (NF2-wildtype) tumors with TRAF7/AKT1/KLF4/SMO mutations represent a potentially targetable subgroup PMID:34433969.

Open questions

  • Precise frequency of SMO mutations within MG2 is not separately enumerated in the corpus PMID:34433969.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:22832583

This page was processed by crosslinker on 2026-05-14. - PMID:23999436

This page was processed by crosslinker on 2026-05-14. - PMID:25855536

This page was processed by crosslinker on 2026-05-14. - PMID:26760213

This page was processed by wiki-cli on 2026-05-14. - PMID:28726821

This page was processed by wiki-cli on 2026-05-15.