title: Characterization of medulloblastoma in Fanconi Anemia: a novel mutation in the BRCA2 gene and SHH molecular subgroup.
abstract: 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.
authors.affiliation: Department of Molecular Medicine Sapienza University, Viale Regina Elena 291, 00161 Rome, Italy.|Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Evelina
authors.initials: E
authors.lastname: Miele
authors.affiliation: Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio 4, 00165 Rome, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Mastronuzzi
authors.affiliation: Department of Molecular Medicine Sapienza University, Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Po
authors.affiliation: Department of Neuroscience and Neurorehabilitation, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio 4, 00165 Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Carai
authors.affiliation: Department of Molecular Medicine Sapienza University, Viale Regina Elena 291, 00161 Rome, Italy.|Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Alfano
authors.affiliation: Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio 4, 00165 Rome, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Serra
authors.affiliation: Department of Radiology, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio 4, 00165 Rome, Italy.
authors.forename: Giovanna Stefania
authors.initials: GS
authors.lastname: Colafati
authors.affiliation: Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio 4, 00165 Rome, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Strocchio
authors.affiliation: Department of Radiological, Oncological and Pathological Science, Sapienza University, Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Manila
authors.initials: M
authors.lastname: Antonelli
authors.affiliation: Department of Radiological, Oncological and Pathological Science, Sapienza University, Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Buttarelli
authors.affiliation: Department of Molecular Medicine Sapienza University, Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Zani
authors.affiliation: Department of Molecular Medicine Sapienza University, Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Ferraro
authors.affiliation: Department of Molecular Medicine Sapienza University, Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Amelia
authors.initials: A
authors.lastname: Buffone
authors.affiliation: Department of Experimental Medicine, Sapienza University, Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Vacca
authors.affiliation: Department of Molecular Medicine Sapienza University, Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Screpanti
authors.affiliation: Department of Radiological, Oncological and Pathological Science, Sapienza University, Viale Regina Elena 291, 00161 Rome, Italy.|Neuromed Institute, Via Atinense 18, 0865 Pozzilli IS, Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Giangaspero
authors.affiliation: Department of Molecular Medicine Sapienza University, Viale Regina Elena 291, 00161 Rome, Italy.|Pasteur Institute/Cenci Bolognetti Foundation, Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giannini
authors.affiliation: Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio 4, 00165 Rome, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Department of Experimental Medicine, Sapienza University, Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferretti
keywords: BRCA2; FANCD1; Fanconi anemia; Medulloblastoma; SHH molecular subgroup