Characterization of medulloblastoma in Fanconi Anemia: a novel mutation in the BRCA2 gene and SHH molecular subgroup

• Published in: Biomarker research 2015-06, Vol.3 (1), p.13, Article 13
• Main Authors: Miele, Evelina, Mastronuzzi, Angela, Po, Agnese, Carai, Andrea, Alfano, Vincenzo, Serra, Annalisa, Colafati, Giovanna Stefania, Strocchio, Luisa, Antonelli, Manila, Buttarelli, Francesca Romana, Zani, Massimo, Ferraro, Sergio, Buffone, Amelia, Vacca, Alessandra, Screpanti, Isabella, Giangaspero, Felice, Giannini, Giuseppe, Locatelli, Franco, Ferretti, Elisabetta
• Format: Article
• Language: English
• Subjects: Care and treatment; Case Report; Case studies; Development and progression; Diagnosis; Disease susceptibility; Fanconi's anemia; Gene mutations; Genes; Genetic aspects; Health aspects; Medulloblastoma; Risk factors
• ISSN: 2050-7771; 2050-7771
• DOI: 10.1186/s40364-015-0038-z

Fanconi Anemia (FA) is an inherited disorder characterized by the variable presence of multiple congenital somatic abnormalities, bone marrow failure and cancer susceptibility. Medulloblastoma (MB) has been described only in few cases of FA with biallelic inactivation in the tumor suppressor gene BRCA2/FANCD1 or its associated gene PALB2/FANCN. We report the case of a patient affected by Fanconi Anemia with Wilms tumor and unusual presentation of two medulloblastomas (MB1 and MB2). We identified a new pathogenetic germline BRCA2 mutation: c.2944_2944delA. Molecular analysis of MBs allowed us to define new features of MB in FA. MBs were found to belong to the Sonic Hedgehog (SHH) molecular subgroup with some differences between MB1 and MB2. We highlighted that MB in FA could share molecular aspects and hemispheric localization with sporadic adult SHH-MB. Our report provides new findings that shed new light on the genetic and molecular pathogenesis of MB in FA patients with implications in the disease management.