ORCID Profile
0000-0002-3108-8311
Current Organisation
Philipps-Universität Marburg
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Publisher: American Association for Cancer Research (AACR)
Date: 26-10-2023
DOI: 10.1158/0008-5472.CAN-22-1492
Abstract: Meta-analyses across cancers show that common germline risk variants affect not only cancer predisposition but the age of cancer onset and burden of somatic alterations, including total mutations and copy-number alterations.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22433402
Abstract: Figures S1–S11, Tables S1–S6, Supplementary Materials and Methods, Supplementary Notes, and Supplementary References
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.C.6514361
Abstract: Abstract Aggregation of genome-wide common risk variants, such as polygenic risk score (PRS), can measure genetic susceptibility to cancer. A better understanding of how common germline variants associate with somatic alterations and clinical features could facilitate personalized cancer prevention and early detection. We constructed PRSs from 14 genome-wide association studies (median i n /i = 64,905) for 12 cancer types by multiple methods and calibrated them using the UK Biobank resources ( i n /i = 335,048). Meta-analyses across cancer types in The Cancer Genome Atlas ( i n /i = 7,965) revealed that higher PRS values were associated with earlier cancer onset and lower burden of somatic alterations, including total mutations, chromosome/arm somatic copy-number alterations (SCNA), and focal SCNAs. This contrasts with rare germline pathogenic variants (e.g., i BRCA1/2 /i variants), showing heterogeneous associations with somatic alterations. Our results suggest that common germline cancer risk variants allow early tumor development before the accumulation of many somatic alterations characteristic of later stages of carcinogenesis. Significance: Meta-analyses across cancers show that common germline risk variants affect not only cancer predisposition but the age of cancer onset and burden of somatic alterations, including total mutations and copy-number alterations. /
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C3OB27302D
Abstract: A series of six new tetravalent ligands (1-6) with two different sets of arms bind to the surface of β-tryptase, a tetrameric enzyme with an A(2)B(2) arrangement of its four monomers and two different binding sites on its protein surface (as suggested by a docking study). Besides proteinogenic amino acids also the guanidiniocarbonyl pyrrole cation (abbreviated as GCP), as an artificial arginine analog, was introduced into the arms of the ligands to investigate its influence on protein surface binding and enzyme inhibition. Furthermore, four ligands (7-10) with four identical arms also containing the GCP group were additionally synthesized to study the influence of the GCP moiety on the inhibition properties compared to related ligands previously identified by us in earlier work. The best ligand from this new series (RWKG)(2)(GCP-LFG)(2) (6) indeed contains the artificial GCP group and with a K(i)-value of 67 nM is two orders of magnitude more efficient than the analogous ligand (RWKG)(2)(RLFG)(2) (1) derived solely from proteinogenic amino acids. Hence, four-armed ligands with two different arms are indeed efficient inhibitors for β-tryptase and the artificial GCP group can improve the binding affinity of this type of ligand to the protein, demonstrating the advantage of tailor-made binding motifs to increase affinity.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22433402.V1
Abstract: Figures S1–S11, Tables S1–S6, Supplementary Materials and Methods, Supplementary Notes, and Supplementary References
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.C.6514361.V1
Abstract: Abstract Aggregation of genome-wide common risk variants, such as polygenic risk score (PRS), can measure genetic susceptibility to cancer. A better understanding of how common germline variants associate with somatic alterations and clinical features could facilitate personalized cancer prevention and early detection. We constructed PRSs from 14 genome-wide association studies (median i n /i = 64,905) for 12 cancer types by multiple methods and calibrated them using the UK Biobank resources ( i n /i = 335,048). Meta-analyses across cancer types in The Cancer Genome Atlas ( i n /i = 7,965) revealed that higher PRS values were associated with earlier cancer onset and lower burden of somatic alterations, including total mutations, chromosome/arm somatic copy-number alterations (SCNA), and focal SCNAs. This contrasts with rare germline pathogenic variants (e.g., i BRCA1/2 /i variants), showing heterogeneous associations with somatic alterations. Our results suggest that common germline cancer risk variants allow early tumor development before the accumulation of many somatic alterations characteristic of later stages of carcinogenesis. Significance: Meta-analyses across cancers show that common germline risk variants affect not only cancer predisposition but the age of cancer onset and burden of somatic alterations, including total mutations and copy-number alterations. /
No related grants have been discovered for Dominik Heider.