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. 2015 Oct 20:5:15454.
doi: 10.1038/srep15454.

Constitutional de novo deletion of the FBXW7 gene in a patient with focal segmental glomerulosclerosis and multiple primitive tumors

Gaia Roversi  1   2 , Chiara Picinelli  3 , Ilaria Bestetti  3   4 , Milena Crippa  3 , Daniela Perotti  5 , Sara Ciceri  5 , Fabiana Saccheri  2 , Paola Collini  6 , Pietro L Poliani  7 , Serena Catania  8 , Bernard Peissel  9 , Fabio Pagni  1 , Silvia Russo  3 , Paolo Peterlongo  10 , Siranoush Manoukian  9 , Palma Finelli  3   4
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Constitutional de novo deletion of the FBXW7 gene in a patient with focal segmental glomerulosclerosis and multiple primitive tumors

Gaia Roversi (V体育平台登录) et al. Sci Rep. .

Abstract

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 VSports手机版. 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. .

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Figures (V体育平台登录)

Figure 1
Figure 1. Identification of a FBXW7 intragenic deletion.
(A) High-resolution aCGH profile showing the presence of a deletion affetting most of the FBXW7 gene coding region. (B) Relative gene expression analysis of FBXW7 mRNA in lymphoblastoid cells of the patient (blue) compared to a pull of ten lymphoblastoid cell lines from normal individuals (red), whose value was set to 1. ** = p < 0.01. (C) SNP haplotype analysis showed four informative SNPs, located in the deleted genomic region, allowing to establish the deletion’s maternal origin.
Figure 2
Figure 2
(A) Cystic lesions characterized by a cubic or flat epithelium. (B) Immunohistochemical analysis for TFE3. (C) TFE3 Break Apart probe FISH on interphase nuclei of the cystic epithelium positive for TFE3 immunostaining. Three cells each with three yellow fused signals, due to lack of traslocation of the 5′ TFE3 red probe from 3′ TFE3 green probe, show each a duplication of a TFE3 allele. (D) Dual color FISH with chromosome X (green) and 18 (red) centromeric probes on interphase nuclei of the cystic epithelium positive for TFE3 immunostaining. Most of the cells show two red chromosome 18 centromeric signals and two to four green X chromosome centromeric signals.
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References (V体育安卓版)

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