Autoren:	Galetzka, Danuta Müller, Tobias Dittrich, Marcus Endres, Miriam Kartal, Nergiz Sinizyn, Olesja Rapp, Steffen Zeller, Tanja Müller, Christian Hankeln, Thomas Scholz-Kreisel, Peter Chorzempa, Heather Mirsch, Johanna Poplawski, Alicia Rossmann, Heidi Spix, Claudia Haaf, Thomas Prawitt, Dirk Marron, Manuela Schmidberger, Heinz
Titel:	Molecular karyotyping and gene expression analysis in childhood cancer patients
Online-Publikationsdatum:	4-Jun-2021
Erscheinungsdatum:	2020
Sprache des Dokuments:	Englisch
Zusammenfassung/Abstract:	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.
DDC-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin FB 10 Biologie
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-5967
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	Journal of molecular medicine 98
Seitenzahl oder Artikelnummer:	1107 1123
Verlag:	Springer
Verlagsort:	Berlin u.a.
Erscheinungsdatum:	2020
ISSN:	1432-1440
URL der Originalveröffentlichung:	https://doi.org/10.1007/s00109-020-01937-4
DOI der Originalveröffentlichung:	10.1007/s00109-020-01937-4
Enthalten in den Sammlungen:	JGU-Publikationen