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Gorlin syndrome and desmoplastic medulloblastoma: Report of 3 cases with unfavorable clinical course and novel mutations
Author(s) -
Gururangan Sridharan,
Robinson Giles,
Ellison David W.,
Wu Gang,
He Xuelian,
Lu Q. Richard,
McLendon Roger,
Grant Gerald,
Driscoll Timothy,
Neuberg Ronnie
Publication year - 2015
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.25560
Subject(s) - medulloblastoma , medicine , pten , ptch1 , missense mutation , loss of heterozygosity , exome sequencing , radiation therapy , cancer research , pathology , oncology , mutation , biology , genetics , gene , hedgehog , pi3k/akt/mtor pathway , apoptosis , allele
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. Pediatr Blood Cancer 2015;62:1855–1858. © 2015 Wiley Periodicals, Inc.