Universität zu Köln

Grimm, Christina ORCID: 0000-0002-4676-8870, Fischer, Axel ORCID: 0000-0001-6130-6984, Farrelly, Angela M., Kalachand, Roshni, Castiglione, Roberta ORCID: 0000-0002-9828-4405, Wasserburger, Elena, Hussong, Michelle, Schultheis, Anne M., Altmueller, Janine, Thiele, Holger, Reinhardt, H. Christian, Hauschulz, Kai, Hennessy, Bryan T., Herwig, Ralf, Lienhard, Matthias, Buettner, Reinhard and Schweiger, Michal R. (2019). Combined Targeted Resequencing of Cytosine DNA Methylation and Mutations of DNA Repair Genes with Potential Use for Poly(ADP-Ribose) Polymerase 1 Inhibitor Sensitivity Testing. J. Mol. Diagn., 21 (2). S. 198 - 214. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1943-7811

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Abstract

Current molecular tumor diagnostics encompass panel sequencing to detect mutations, copy number alterations, and rearrangements. However, tumor suppressor genes can also be inactivated by methylation within their promoter region. These epigenetic alterations are so far rarely assessed in the clinical setting. Therefore, we established the AllCap protocol facilitating the combined detection of mutations and DNA methylation at the coding and promoter regions of 342 DNA repair genes in one experiment. We demonstrate the use of the protocol by applying it to ovarian cancer cell lines with different responsiveness to poly(ADP-ribose) polymerase inhibition. BRCA1, ATM, ATR, and EP300 mutations and methylation of the BRCA1 promoter were detected as potential predictors for therapy response. The required amount of input DNA was optimized, and the application to formalin-fixed, paraffin-embedded tissue samples was verified to improve the clinical applicability. Thus, by adding DNA methylation values to panel resequencings, the ALICap assay will add another important level of information to clinical tests and will improve stratification of patients for systemic therapies.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Grimm, Christina UNSPECIFIED orcid.org/0000-0002-4676-8870 UNSPECIFIED Fischer, Axel UNSPECIFIED orcid.org/0000-0001-6130-6984 UNSPECIFIED Farrelly, Angela M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kalachand, Roshni UNSPECIFIED UNSPECIFIED UNSPECIFIED Castiglione, Roberta UNSPECIFIED orcid.org/0000-0002-9828-4405 UNSPECIFIED Wasserburger, Elena UNSPECIFIED UNSPECIFIED UNSPECIFIED Hussong, Michelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Schultheis, Anne M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinhardt, H. Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Hauschulz, Kai UNSPECIFIED UNSPECIFIED UNSPECIFIED Hennessy, Bryan T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Herwig, Ralf UNSPECIFIED UNSPECIFIED UNSPECIFIED Lienhard, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Schweiger, Michal R. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-155254
DOI:	10.1016/j.jmoldx.2018.10.007
Journal or Publication Title:	J. Mol. Diagn.
Volume:	21
Number:	2
Page Range:	S. 198 - 214
Date:	2019
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1943-7811
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INDUCED APOPTOTIC PATHWAY; EPIGENETIC CHANGES; CANCER; RESISTANCE; GENOMICS; KEGG; ENCYCLOPEDIA; ASSOCIATION; CARCINOMA; RESOURCE Multiple languages Pathology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15525