Internet Archive Scholar

Genetic and epigenetic analyses guided by high resolution whole-genome SNP array reveals a possible role of CHEK2 in Wilms tumour susceptibility

Sara Ciceri, Beatrice Gamba, Paola Corbetta, Patrizia Mondini, Monica Terenziani, Serena Catania, Marilina Nantron, Maurizio Bianchi, Paolo D'Angelo, Federica Torri, Fabio Macciardi, Paola Collini (+7 others)
2018 OncoTarget  

Preserved Fulltext

Web Archive Capture PDF (2.6 MB)
https://web.archive.org/web/20191114234318/http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=26123&path%5B%5D=81466

A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2019; you can also visit the original URL. The file type is application/pdf.

Wilms tumour (WT), the most frequent malignant childhood renal tumour, shows a high degree of genetic and epigenetic heterogeneity. Loss of imprinting on chromosome 11p15 is found in a large fraction of cases and mutations in a few genes, including WT1, CTNNB1, WTX, TP53 and, more recently, SIX1, SIX2 and micro RNA processing genes (miRNAPGs), have been observed. However, these alterations are not sufficient to describe the entire spectrum of genetic defects underlying WT development. We
more » ... ed data obtained from a previously performed genome-wide single nucleotide polymorphism (SNP) array analysis on 96 WT samples. By selecting focal regions commonly involved in chromosomal anomalies, we identified genes with a possible role in WT development, based on the prior knowledge of their biological relevance, including MYCN, DIS3L2, MIR562, HACE1, GLI3, CDKN2A and CDKN2B, PALB2, and CHEK2. The MYCN hotspot mutation c.131C>T was detected in seven cases (7.3%). Full sequencing of the remaining genes disclosed 16 rare missense variants and a splicing mutation. Most of these were present at the germline level. Promoter analysis of HACE1, CDKN2A and CDKN2B disclosed partial methylation affecting HACE1 in a consistent fraction of cases (85%). Interestingly, of the four missense variants identified in CHEK2, three were predicted to be deleterious by in silico analyses, while an additional variant was observed to alter mRNA splicing, generating a functionally defective protein. Our study adds additional information on putative WT genes, and adds evidences involving CHEK2 in WT susceptibility.
doi:10.18632/oncotarget.26123 fatcat:lm7f2eigunht7ejyhrkfttx5lu
Open Access
Citation

Sara Ciceri, Beatrice Gamba, Paola Corbetta, Patrizia Mondini, Monica Terenziani, Serena Catania, Marilina Nantron, Maurizio Bianchi, Paolo D'Angelo, Federica Torri, Fabio Macciardi, Paola Collini, Martina Di Martino, Fraia Melchionda, Andrea Di Cataldo, Filippo Spreafico, Paolo Radice, Daniela Perotti, on behalf of the AIEOP study group. "Genetic and epigenetic analyses guided by high resolution whole-genome SNP array reveals a possible role of CHEK2 in Wilms tumour susceptibility." OncoTarget 9.75 (2018)