Loss of the PTCH1 tumor suppressor defines a new subset of plexiform fibromyxoma

Sudeep Banerjee, Christopher L. Corless, Markku M. Miettinen, Sangkyu Noh, Rowan Ustoy, Jessica L. Davis, Chih Min Tang, Mayra Yebra, Adam M. Burgoyne, Jason K. Sicklick

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Background: Plexiform fibromyxoma (PF) is a rare gastric tumor often confused with gastrointestinal stromal tumor. These so-called "benign" tumors often present with upper GI bleeding and gastric outlet obstruction. It was recently demonstrated that approximately one-third of PF have activation of the GLI1 oncogene, a transcription factor in the hedgehog (Hh) pathway, via a MALAT1-GLI1 fusion protein or GLI1 up-regulation. Despite this discovery, the biology of most PFs remains unknown. Methods: Next generation sequencing (NGS) was performed on formalin-fixed paraffin-embedded (FFPE) samples of PF specimens collected from three institutions (UCSD, NCI and OHSU). Fresh frozen tissue from one tumor was utilized for in vitro assays, including quantitative RT-PCR and cell viability assays following drug treatment. Results: Eight patients with PF were identified and 5 patients' tumors were analyzed by NGS. An index case had a mono-allelic PTCH1 deletion of exons 15-24 and a second case, identified in a validation cohort, also had a PTCH1 gene loss associated with a suspected long-range chromosome 9 deletion. Building on the role of Hh signaling in PF, PTCH1, a tumor suppressor protein, functions upstream of GLI1. Loss of PTCH1 induces GLI1 activation and downstream gene transcription. Utilizing fresh tissue from the index PF case, RT-qPCR analysis demonstrated expression of Hh pathway components, SMO and GLI1, as well as GLI1 transcriptional targets, CCND1 and HHIP. In turn, short-term in vitro treatment with a Hh pathway inhibitor, sonidegib, resulted in dose-dependent cell killing. Conclusions: For the first time, we report a novel association between PTCH1 inactivation and the development of plexiform fibromyxoma. Hh pathway inhibition with SMO antagonists may represent a target to study for treating a subset of plexiform fibromyxomas.

Original languageEnglish (US)
Article number246
JournalJournal of translational medicine
Issue number1
StatePublished - Jul 30 2019


  • GLI1
  • Gastric mass
  • Gastrointestinal stromal tumor
  • Hedgehog pathway
  • Next generation sequencing
  • Patched 1
  • SMO inhibitor
  • Sonidegib
  • Submucosal tumor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'Loss of the PTCH1 tumor suppressor defines a new subset of plexiform fibromyxoma'. Together they form a unique fingerprint.

Cite this