Emmert, Steffen

[["dc.bibliographiccitation.artnumber","e1006248"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","PLOS Genetics"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Rump, Andreas"],["dc.contributor.author","Benet-Pages, Anna"],["dc.contributor.author","Schubert, Steffen"],["dc.contributor.author","Kuhlmann, Jan Dominik"],["dc.contributor.author","Janavičius, Ramūnas"],["dc.contributor.author","Macháčková, Eva"],["dc.contributor.author","Foretová, Lenka"],["dc.contributor.author","Kleibl, Zdenek"],["dc.contributor.author","Lhota, Filip"],["dc.contributor.author","Zemankova, Petra"],["dc.contributor.author","Betcheva-Krajcir, Elitza"],["dc.contributor.author","Mackenroth, Luisa"],["dc.contributor.author","Hackmann, Karl"],["dc.contributor.author","Lehmann, Janin"],["dc.contributor.author","Nissen, Anke"],["dc.contributor.author","DiDonato, Nataliya"],["dc.contributor.author","Opitz, Romy"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Kast, Karin"],["dc.contributor.author","Wimberger, Pauline"],["dc.contributor.author","Holinski-Feder, Elke"],["dc.contributor.author","Emmert, Steffen"],["dc.contributor.author","Schröck, Evelin"],["dc.contributor.author","Klink, Barbara"],["dc.date.accessioned","2019-07-09T11:42:49Z"],["dc.date.available","2019-07-09T11:42:49Z"],["dc.date.issued","2016"],["dc.description.abstract","The increasing application of gene panels for familial cancer susceptibility disorders will probably lead to an increased proposal of susceptibility gene candidates. Using ERCC2 DNA repair gene as an example, we show that proof of a possible role in cancer susceptibility requires a detailed dissection and characterization of the underlying mutations for genes with diverse cellular functions (in this case mainly DNA repair and basic cellular transcription). In case of ERCC2, panel sequencing of 1345 index cases from 587 German, 405 Lithuanian and 353 Czech families with breast and ovarian cancer (BC/OC) predisposition revealed 25 mutations (3 frameshift, 2 splice-affecting, 20 missense), all absent or very rare in the ExAC database. While 16 mutations were unique, 9 mutations showed up repeatedly with population-specific appearance. Ten out of eleven mutations that were tested exemplarily in cell-based functional assays exert diminished excision repair efficiency and/or decreased transcriptional activation capability. In order to provide evidence for BC/OC predisposition, we performed familial segregation analyses and screened ethnically matching controls. However, unlike the recently published RECQL example, none of our recurrent ERCC2 mutations showed convincing co-segregation with BC/OC or significant overrepresentation in the BC/OC cohort. Interestingly, we detected that some deleterious founder mutations had an unexpectedly high frequency of > 1% in the corresponding populations, suggesting that either homozygous carriers are not clinically recognized or homozygosity for these mutations is embryonically lethal. In conclusion, we provide a useful resource on the mutational landscape of ERCC2 mutations in hereditary BC/OC patients and, as our key finding, we demonstrate the complexity of correct interpretation for the discovery of “bonafide” breast cancer susceptibility genes."],["dc.identifier.doi","10.1371/journal.pgen.1006248"],["dc.identifier.pmid","27504877"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13771"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58754"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1553-7404"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Identification and Functional Testing of ERCC2 Mutations in a Multi-national Cohort of Patients with Familial Breast- and Ovarian Cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","353"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Archives of Dermatological Research"],["dc.bibliographiccitation.lastpage","361"],["dc.bibliographiccitation.volume","304"],["dc.contributor.author","Schaefer, Annika"],["dc.contributor.author","Emmert, Steffen"],["dc.contributor.author","Kruppa, Jochen"],["dc.contributor.author","Schubert, Steffen"],["dc.contributor.author","Tzvetkov, Mladen"],["dc.contributor.author","Moessner, Rotraut"],["dc.contributor.author","Reich, Kristian"],["dc.contributor.author","Berking, Carola"],["dc.contributor.author","Volkenandt, Matthias"],["dc.contributor.author","Pfoehler, Claudia"],["dc.contributor.author","Schoen, Michael Peter"],["dc.contributor.author","Vogt, Thomas"],["dc.contributor.author","Koenig, Inke R."],["dc.contributor.author","Reichrath, Joerg"],["dc.date.accessioned","2018-11-07T09:08:44Z"],["dc.date.available","2018-11-07T09:08:44Z"],["dc.date.issued","2012"],["dc.description.abstract","Melanoma is one of the most aggressive human cancers. The vitamin D system contributes to the pathogenesis and prognosis of malignancies including cutaneous melanoma. An expression of the vitamin D receptor (VDR) and an anti-proliferative effect of vitamin D in melanocytes and melanoma cells have been shown in vitro. Studies examining associations of polymorphisms in genes coding for vitamin D metabolism-related proteins (1 alpha-hydroxylase [CYP27B1], 1,25(OH)(2)D-24hydroxylase [CYP24A1], vitamin D-binding protein [VDBP]) and cancer risk are scarce, especially with respect to melanoma. Mainly VDR polymorphisms regarding melanoma risk and prognosis were examined although other vitamin D metabolism-related genes may also be crucial. In our hospital-based case-control study including 305 melanoma patients and 370 healthy controls single nucleotide polymorphisms in the genes CYP27B1 (rs4646536), CYP24A1 (rs927650), VDBP (rs1155563, rs7041), and VDR (rs757343, rs731236, rs2107301, rs7975232) were analyzed for their association with melanoma risk and prognosis. Except VDR rs731236 and VDR rs2107301, the other six polymorphisms have not been analyzed regarding melanoma before. To further improve the prevention as well as the treatment of melanoma, it is important to identify further genetic markers for melanoma risk as well as prognosis in addition to the crude phenotypic, demographic, and environmental markers used in the clinic today. A panel of genetic risk markers could help to better identify individuals at risk for melanoma development or worse prognosis. We, however, found that none of the polymorphisms tested was associated with melanoma risk as well as prognosis in logistic and linear regression models in our study population."],["dc.identifier.doi","10.1007/s00403-012-1243-3"],["dc.identifier.isi","000305680200003"],["dc.identifier.pmid","22576141"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8093"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26096"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0340-3696"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","No association of vitamin D metabolism-related polymorphisms and melanoma risk as well as melanoma prognosis: a case-control study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]