<em>PTCH1</em> mutant small cell glioblastoma in a patient with Gorlin syndrome: A case report

Dorsey,John T.; Mott,Ryan T.; Lack,Christopher M.; Britt,Nicholas; Ramkissoon,Shakti H.; Morris,Bonny B.; Carter,Annette; Detroye,Alisha T.; Chan,Michael; Tatter,Stephen; Lesser,Glenn J.

doi:10.3892/ol.2022.13446

PTCH1 mutant small cell glioblastoma in a patient with Gorlin syndrome: A case report

Authors:
- John T. Dorsey
- Ryan T. Mott
- Christopher M. Lack
- Nicholas Britt
- Shakti H. Ramkissoon
- Bonny B. Morris
- Annette Carter
- Alisha T. Detroye
- Michael Chan
- Stephen Tatter
- Glenn J. Lesser
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Affiliations: Department of Hematology‑Oncology, Cone Health Cancer Center, Greensboro, NC 27403, USA, Department of Pathology, Wake Forest School of Medicine, Winston‑Salem, NC 27157, USA, Department of Radiology, Wake Forest School of Medicine, Winston‑Salem, NC 27157, USA, Department of Pathology, Foundation Medicine, Morrisville, NC 27560, USA, Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston‑Salem, NC 27157, USA, Department of Internal Medicine, Section on Hematology and Oncology, Wake Forest School of Medicine, Winston‑Salem, NC 27157, USA, Department of Radiation Oncology, Wake Forest School of Medicine, Winston‑Salem, NC 27157, USA, Department of Neurosurgery, Wake Forest School of Medicine, Winston‑Salem, NC 27157, USA
Published online on: July 27, 2022 https://doi.org/10.3892/ol.2022.13446
Article Number: 326
Copyright: © Dorsey et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gorlin syndrome or nevoid basal cell carcinoma syndrome is a rare genetic disease characterized by predisposition to congenital defects, basal cell carcinomas and medulloblastoma. The syndrome results from a heritable mutation in PATCHED1 (PTCH1), causing constitutive activation of the Hedgehog pathway. The present study described a patient with Gorlin syndrome who presented early in life with characteristic basal cell carcinomas and later developed a small cell glioblastoma (GBM), World Health Organization grade IV, associated with a Patched 1 (PTCH1) N97fs*43 mutation. Comprehensive genomic profiling of GBM tissues also revealed multiple co‑occurring alterations including cyclin‑dependent kinase 4 (CDK4) amplification, receptor tyrosine‑protein kinase 3 (ERBB3) amplification, a fibroblast growth factor receptor 1 and transforming acidic coiled‑coil containing protein 1 (FGFR1‑TACC1) fusion, zinc finger protein (GLI1) amplification, E3 ubiquitin‑protein ligase (MDM2) amplification and spectrin α chain, erythrocytic 1 (SPTA1) T1151fs*24. After the biopsy, imaging revealed extensive leptomeningeal enhancement intracranially and around the cervical spinal cord due to leptomeningeal disease. The patient underwent craniospinal radiation followed by 6 months of adjuvant temozolomide (150 mg/m²) with good response. She was then treated with vismodegib for 11 months, first combined with temozolomide and then with bevacizumab, until disease progression was noted on MRI, with no significant toxicities associated with the combination therapy. She received additional therapies but ultimately succumbed to the disease four months later. The current study presents the first documentation in the literature of a primary (non‑radiation induced) glioblastoma secondary to Gorlin syndrome. Based on this clinical experience, vismodegib should be considered in combination with standard‑of‑care therapies for patients with known Gorlin syndrome‑associated glioblastomas and sonic hedgehog pathway mutations.

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