| Autor: |
Danuta G; Department of Radiation Oncology and Radiation Therapy, University Medical Centre, Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 63, 55131, Mainz, Germany. Danuta.Galetzka@unimedizin-mainz.de., Tobias M; Bioinformatics Department, Julius Maximilians University, Würzburg, Germany., Marcus D; Bioinformatics Department, Julius Maximilians University, Würzburg, Germany., Miriam E; Department of Radiation Oncology and Radiation Therapy, University Medical Centre, Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 63, 55131, Mainz, Germany., Nergiz K; Department of Radiation Oncology and Radiation Therapy, University Medical Centre, Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 63, 55131, Mainz, Germany., Olesja S; Department of Radiation Oncology and Radiation Therapy, University Medical Centre, Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 63, 55131, Mainz, Germany., Steffen R; Institute of Organismal and Molecular Evolution, Molecular Genetics and Genome Analysis, Johannes Gutenberg University, Mainz, Germany.; Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Centre, Mainz, Germany., Tanja Z; University Heart & Vascular Center, Clinic for Cardiology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.; Dzhk (Deutsches Zentrum für Herzkreislauf-Forschung), Standort Hamburg, Lübeck, Kiel, Hamburg, Germany., Christian M; University Heart & Vascular Center, Clinic for Cardiology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.; Dzhk (Deutsches Zentrum für Herzkreislauf-Forschung), Standort Hamburg, Lübeck, Kiel, Hamburg, Germany., Thomas H; Institute of Organismal and Molecular Evolution, Molecular Genetics and Genome Analysis, Johannes Gutenberg University, Mainz, Germany., Peter SK; Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Centre, Mainz, Germany., Heather C; Center for Pediatrics and Adolescent Medicine, University Medical Centre, Mainz, Germany.; Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany., Johanna M; Radiation Biology and DNA Repair, University of Technology, Darmstadt, Germany., Alicia P; Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Centre, Mainz, Germany., Heidi R; Institute of Clinical Chemistry and Laboratory Medicine, University Medical Centre, Mainz, Germany., Claudia S; German Childhood Cancer Registry, Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Centre, Mainz, Germany., Thomas H; Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany., Dirk P; Center for Pediatrics and Adolescent Medicine, University Medical Centre, Mainz, Germany., Manuela M; Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany., Heinz S; Department of Radiation Oncology and Radiation Therapy, University Medical Centre, Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 63, 55131, Mainz, Germany. |
| Abstrakt: |
The genetic etiology of sporadic childhood cancer cases remains unclear. We recruited a cohort of 20 patients who survived a childhood malignancy and then developed a second primary cancer (2N), and 20 carefully matched patients who survived a childhood cancer without developing a second malignancy (1N). Twenty matched cancer-free (0N) and additional 1000 (0N) GHS participants served as controls. Aiming to identify new candidate loci for cancer predisposition, we compared the genome-wide DNA copy number variations (CNV) with the RNA-expression data obtained after in vitro irradiation of primary fibroblasts. In 2N patients, we detected a total of 142 genes affected by CNV. A total of 53 genes of these were not altered in controls. Six genes (POLR3F, SEC23B, ZNF133, C16orf45, RRN3, and NTAN1) that we found to be overexpressed after irradiation were also duplicated in the genome of the 2N patients. For the 1N collective, 185 genes were affected by CNV and 38 of these genes were not altered in controls. Five genes (ZCWPW2, SYNCRIP, DHX30, DHRS4L2, and THSD1) were located in duplicated genomic regions and exhibited altered RNA expression after irradiation. One gene (ABCC6) was partially duplicated in one 1N and one 2N patient. Analysis of methylation levels of THSD1 and GSTT2 genes which were detected in duplicated regions and are frequently aberrantly methylated in cancer showed no changes in patient's fibroblasts. In summary, we describe rare and radiation-sensitive genes affected by CNV in childhood sporadic cancer cases, which may have an impact on cancer development. KEY MESSAGES: • Rare CNV's may have an impact on cancer development in sporadic, non-familial, non-syndromic childhood cancer cases. • In our cohort, each patient displayed a unique pattern of cancer-related gene CNVs, and only few cases shared similar CNV. • Genes that are transcriptionally regulated after radiation can be located in CNVs in cancer patients and controls. • THSD1 and GSTT2 methylation is not altered by CNV. |
Full text from SpringerLink