TY - JOUR
T1 - Disseminated medulloblastoma in a child with germline BRCA2 6174delT mutation and without Fanconi anemia
AU - Xu, Jingying
AU - Margol, Ashley Sloane
AU - Shukla, Anju
AU - Ren, Xiuhai
AU - Finlay, Jonathan L.
AU - Krieger, Mark D.
AU - Gilles, Floyd H.
AU - Couch, Fergus J.
AU - Aziz, Meraj
AU - Fung, Eric T.
AU - Asgharzadeh, Shahab
AU - Barrett, Michael T.
AU - Erdreich-Epstein, Anat
N1 - Publisher Copyright:
© 2015 Xu, Margol, Shukla, Ren, Finlay, Krieger, Gilles, Couch, Aziz, Fung, Asgharzadeh, Barrett and Erdreich-Epstein.
PY - 2015
Y1 - 2015
N2 - Medulloblastoma, the most common malignant brain tumor in children, occurs with increased frequency in individuals with Fanconi anemia who have biallelic germline mutations in BRCA2. We describe an 8-year-old child who had disseminated anaplastic medulloblastoma and a deleterious heterozygous BRCA2 6174delT germline mutation. Molecular profiling was consistent with Group 4 medulloblastoma. The posterior fossa mass was resected and the patient received intensive chemotherapy and craniospinal irradiation. Despite this, the patient succumbed to a second recurrence of his medulloblastoma, which presented 8 months after diagnosis as malignant pleural and peritoneal effusions. Continuous medulloblastoma cell lines were isolated from the original tumor (CHLA-01-MED) and the malignant pleural effusion (CHLA-01R-MED). Here, we provide their analyses, including in vitro and in vivo growth, drug sensitivity, comparative genomic hybridization, and next generation sequencing analysis. In addition to the BRCA2 6174delT, the medulloblastoma cells had amplification of MYC, deletion at Xp11.2, and isochromosome 17, but no structural variations or overexpression of GFI1 or GFI1B. To our knowledge, this is the first pair of diagnosis/recurrence medulloblastoma cell lines, the only medulloblastoma cell lines with BRCA2 6174delT described to date, and the first reported case of a child with medulloblastoma associated with a germline BRCA2 6174delT who did not also have Fanconi anemia.
AB - Medulloblastoma, the most common malignant brain tumor in children, occurs with increased frequency in individuals with Fanconi anemia who have biallelic germline mutations in BRCA2. We describe an 8-year-old child who had disseminated anaplastic medulloblastoma and a deleterious heterozygous BRCA2 6174delT germline mutation. Molecular profiling was consistent with Group 4 medulloblastoma. The posterior fossa mass was resected and the patient received intensive chemotherapy and craniospinal irradiation. Despite this, the patient succumbed to a second recurrence of his medulloblastoma, which presented 8 months after diagnosis as malignant pleural and peritoneal effusions. Continuous medulloblastoma cell lines were isolated from the original tumor (CHLA-01-MED) and the malignant pleural effusion (CHLA-01R-MED). Here, we provide their analyses, including in vitro and in vivo growth, drug sensitivity, comparative genomic hybridization, and next generation sequencing analysis. In addition to the BRCA2 6174delT, the medulloblastoma cells had amplification of MYC, deletion at Xp11.2, and isochromosome 17, but no structural variations or overexpression of GFI1 or GFI1B. To our knowledge, this is the first pair of diagnosis/recurrence medulloblastoma cell lines, the only medulloblastoma cell lines with BRCA2 6174delT described to date, and the first reported case of a child with medulloblastoma associated with a germline BRCA2 6174delT who did not also have Fanconi anemia.
KW - BRCA2 6174delT
KW - Fanconi anemia
KW - Group 4 medulloblastoma
KW - MYC
KW - Medulloblastoma cell lines
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U2 - 10.3389/fonc.2015.00191
DO - 10.3389/fonc.2015.00191
M3 - Article
AN - SCOPUS:84940990404
SN - 2234-943X
VL - 5
JO - Frontiers in Oncology
JF - Frontiers in Oncology
IS - Aug
M1 - 191
ER -