Gorlin syndrome and desmoplastic medulloblastoma: Report of 3 cases with unfavorable clinical course and novel mutations

Sridharan Gururangan, Giles Robinson, David W. Ellison, Gang Wu, Xuelian He, Q. Richard Lu, Roger Mclendon, Gerald Grant, Timothy Driscoll, Ronnie Neuberg

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

We present three cases of genetically confirmed Gorlin syndrome with desmoplastic medulloblastoma (DMB) in whom tumor recurred despite standard therapy. One patient was found to have a novel germline missense PTCH1 mutation. Molecular analysis of recurrent tumor using fluorescent in situ hybridization (FISH) revealed PTEN and/ or PTCH1 loss in 2 patients. Whole exome sequencing (WES) of tumor in one patient revealed loss of heterozygosity of PTCH1 and a mutation of GNAS gene in its non-coding 3' -untranslated region (UTR) with corresponding decreased protein expression. While one patient died despite high-dose chemotherapy (HDC) plus stem cell rescue (ASCR) and palliative radiotherapy, two patients are currently alive for 18+ and 120+ months respectively following retrieval therapy that did not include irradiation. Infants with DMB and GS should be treated aggressively with chemotherapy at diagnosis to prevent relapse but radiotherapy should be avoided. The use of molecular prognostic markers for DMB should be routinely used to identify the subset of tumors that might have an aggressive course.

Original languageEnglish (US)
Pages (from-to)1855-1858
Number of pages4
JournalPediatric Blood and Cancer
Volume62
Issue number10
DOIs
StatePublished - Oct 1 2015

Keywords

  • Clinical features
  • Gorlin syndrome
  • Medulloblastoma
  • Mutation
  • PTCH
  • Whole genome sequencing

ASJC Scopus subject areas

  • Oncology
  • Pediatrics, Perinatology, and Child Health
  • Hematology

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    Gururangan, S., Robinson, G., Ellison, D. W., Wu, G., He, X., Lu, Q. R., Mclendon, R., Grant, G., Driscoll, T., & Neuberg, R. (2015). Gorlin syndrome and desmoplastic medulloblastoma: Report of 3 cases with unfavorable clinical course and novel mutations. Pediatric Blood and Cancer, 62(10), 1855-1858. https://doi.org/10.1002/pbc.25560