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

Journal of Translational Medicine
Sudeep BanerjeeJason K Sicklick

Abstract

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. 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. 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 downstr...Continue Reading

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Citations

Mar 5, 2020·Molecular Cancer Therapeutics·Sudeep BanerjeePartha Ray
Jan 1, 2021·Histopathology·David J Papke, Jason L Hornick
May 28, 2021·World Journal of Gastrointestinal Oncology·Mustafa Erdem ArslanHwajeong Lee
Aug 10, 2021·The Journal of International Medical Research·Shaofei MaJun Lin

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Methods Mentioned

BETA
RNASeq
electrophoresis
Assay
PCR

Software Mentioned

RNASeq
Prism GraphPad
GraphPad
GeneTrails
ClinVar
UCSC Genome Browser

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