Genetic characterization of Polish ccRCC patients: somatic mutation analysis of PBRM1, BAP1 and KDMC5, genomic SNP array analysis in tumor biopsy and preliminary results of chromosome aberrations analysis in plasma cell free DNA
Metrics: PDF 1469 views | HTML 1955 views | ?
Katarzyna Kluzek1,*, Malgorzata I. Srebniak2,*, Weronika Majer3, Agnieszka Ida4, Tomasz Milecki4, Kinga Huminska3,5, Robert M. van der Helm2, Adrian Silesian1, Tomasz M. Wrzesinski3, Jacek Wojciechowicz5, Berna H. Beverloo2, Zbigniew Kwias4, Hans A.R. Bluyssen1, Joanna Wesoly3
1Department of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University in Poznan, 61-614 Poznan, Poland
2Department of Clinical Genetics, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands
3Laboratory of High Throughput Technologies, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University in Poznan, 61-614 Poznan, Poland
4Department of Urology and Urological Oncology, Poznan University of Medical Sciences, 61-285 Poznan, Poland
5Genomic Laboratory, DNA Research Center, 61-612 Poznan, Poland
*These authors have contributed equally to this work
Joanna Wesoly, email: firstname.lastname@example.org
Keywords: ccRCC, SNP microarrays, SNV, chromatin remodeling, cell free DNA
Received: July 08, 2016 Accepted: January 10, 2017 Published: February 15, 2017
Background: Mutation analysis and cytogenetic testing in clear cell renal cell carcinoma (ccRCC) is not yet implemented in a routine diagnostics of ccRCC.
Material and methods: We characterized the chromosomal alterations in 83 ccRCC tumors from Polish patients using whole genome SNP genotyping assay. Moreover, the utility of next generation sequencing of cell free DNA (cfDNA) in patients plasma as a potential tool for non-invasive cytogenetic analysis was tested. Additionally, tumor specific somatic mutations in PBRM1, BAP1 and KDM5C were determined.
Results: We confirmed a correlation between deletions at 9p and higher tumor size, and deletion of chromosome 20 and the survival time. In Fuhrman grade 1, only aberrations of 3p and 8p deletion, gain of 5q and 13q and gains of chromosome 7 and 16 were present. The number of aberrations increased with Fuhrman grade, all chromosomes displayed cytogenetic changes in G3 and G4. ccRCC specific chromosome aberrations were observed in cfDNA, although discrepancies were found between cfDNA and tumor samples. In total 12 common and 94 rare variants were detected in PBRM1, BAP1 and KDM5C, with four potentially pathogenic variants. We observed markedly lower mutation load in PBRM1.
Conclusions: Cytogenetic analysis of cfDNA may allow more accurate diagnosis of tumor aberrations and therefore the correlation between the chromosome aberrations in cfDNA and clinical outcome should be studied in larger cohorts. The functional studies on in BAP1, KDM5C, PBRM1 mutations in large, independent sample set would be necessary for the assessment of their prognostic and diagnostic potential.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.