Constitutional de novo deletion of the FBXW7 gene in a patient with focal segmental glomerulosclerosis and multiple primitive tumors.
Multiple primary malignant neoplasms are rare entities in the clinical setting, but represent an important issue in the clinical management of patients since they could be expression of a genetic predisposition to malignancy. A high resolution genome wide array CGH led us to identify the first case of a de novo constitutional deletion confined to the FBXW7 gene, a well known tumor suppressor, in a patient with a syndromic phenotype characterized by focal segmental glomerulosclerosis and multiple primary early/atypical onset tumors, including Hodgkin's lymphoma, Wilms tumor and breast cancer. Other genetic defects may be associated with patient's phenotype. In this light, constitutional mutations at BRCA1, BRCA2, TP53, PALB2 and WT1 genes were excluded by performing sequencing and MLPA analysis; similarly, we ruled out constitutional abnormalities at the imprinted 11p15 region by methylation specific -MLPA assay. Our observations sustain the role of FBXW7 as cancer predisposition gene and expand the spectrum of its possible associated diseases.
Department of Surgery and Translational Medicine, University of Milano-Bicocca, Monza, Italy.|Medical Genetics Lab, San Gerardo Hospital, Monza, Italy.
Gaia
G
Roversi
Medical Cytogenetics and Molecular Genetics Lab, IRCCS Istituto Auxologico Italiano, Milan, Italy.
Chiara
C
Picinelli
Medical Cytogenetics and Molecular Genetics Lab, IRCCS Istituto Auxologico Italiano, Milan, Italy.|Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy.
Ilaria
I
Bestetti
Medical Cytogenetics and Molecular Genetics Lab, IRCCS Istituto Auxologico Italiano, Milan, Italy.
Milena
M
Crippa
Molecular Bases of Genetic Risk and Genetic Testing Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Daniela
D
Perotti
Molecular Bases of Genetic Risk and Genetic Testing Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Sara
S
Ciceri
Medical Genetics Lab, San Gerardo Hospital, Monza, Italy.
Fabiana
F
Saccheri
Soft Tissue and Bone Pathology, Histopathology and Pediatric Pathology Unit, Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Paola
P
Collini
Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Pietro L
PL
Poliani
Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Serena
S
Catania
Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Bernard
B
Peissel
Department of Surgery and Translational Medicine, University of Milano-Bicocca, Monza, Italy.
Fabio
F
Pagni
Medical Cytogenetics and Molecular Genetics Lab, IRCCS Istituto Auxologico Italiano, Milan, Italy.
Silvia
S
Russo
IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy.
Paolo
P
Peterlongo
Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Siranoush
S
Manoukian
Medical Cytogenetics and Molecular Genetics Lab, IRCCS Istituto Auxologico Italiano, Milan, Italy.|Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy.
Palma
P
Finelli
D000328:Adult; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D044783:F-Box Proteins / Q000235:genetics*; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D017353:Gene Deletion; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005923:Glomerulosclerosis, Focal Segmental / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D059785:Karyotype; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; C069203:TFE3 protein, human; D044767:Ubiquitin-Protein Ligases