Universität zu Köln

Endris, Volker, Stenzinger, Albrecht, Pfarr, Nicole, Penzel, Roland, Moebs, Markus, Lenze, Dido, Darb-Esfahani, Silvia, Hummel, Michael, Jung, Andreas, Lehmann, Ulrich, Kreipe, Hans, Kirchner, Thomas, Buettner, Reinhard, Jochum, Wolfram, Hoefler, Gerald, Dietel, Manfred, Weichert, Wilko and Schirmacher, Peter (2016). NGS-based BRCA1/2 mutation testing of high-grade serous ovarian cancer tissue: results and conclusions of the first international round robin trial. Virchows Arch., 468 (6). S. 697 - 706. NEW YORK: SPRINGER. ISSN 1432-2307

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Abstract

With the approval of olaparib as monotherapy treatment in platinum-sensitive, relapsed high-grade serous ovarian cancer by the European Medical Agency (EMA), comprehensive genotyping of BRCA1 and BRCA2 in tumor tissue has become a mandatory pre-therapeutic test. This requires significant advances in routine tumor test methodologies due to the large size of both genes and the lack of mutational hot spots. Classical focused screening approaches, like Sanger sequencing, do not allow for a sensitive, rapid, and economic analysis of tumor tissue. Next-generation sequencing (NGS) approaches employing targeted panels for BRCA1/2 to interrogate formalin-fixed and paraffin-embedded tumor samples from either surgical resection or biopsy specimens can overcome these limitations. Although focused NGS methods have been implemented by few centers in routine molecular diagnostics for the analysis of some druggable oncogenic mutations, the reliable diagnostic testing of the entire coding regions of BRCA1 and BRCA2 was a new challenge requiring extensive technological improvement and quality management. Here, we describe the implementation and results of the first round robin trial for BRCA1/2 mutation testing in tumor tissue that was conducted in central Europe on May 2015, shortly after the approval and prior to the official release of olaparib. The high success rate of 81 % (21/26 test centers) demonstrates that BRCA1/2 multicenter mutation testing is well feasible in FFPE tumor tissue, extending to other tumor entities beyond ovarian cancer. The high number of test centers passing the trial demonstrates the success of the concerted efforts by German, Swiss, and Austrian pathology centers to ensure quality-controlled NGS-based testing and proves the potential of this technology in routine molecular pathology. On the basis of our results, we provide recommendations for predictive testing of tumor tissue for BRCA1/2 to clinical decision making in ovarian cancer patients.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Endris, Volker UNSPECIFIED UNSPECIFIED UNSPECIFIED Stenzinger, Albrecht UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfarr, Nicole UNSPECIFIED UNSPECIFIED UNSPECIFIED Penzel, Roland UNSPECIFIED UNSPECIFIED UNSPECIFIED Moebs, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Lenze, Dido UNSPECIFIED UNSPECIFIED UNSPECIFIED Darb-Esfahani, Silvia UNSPECIFIED UNSPECIFIED UNSPECIFIED Hummel, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Jung, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehmann, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreipe, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirchner, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Jochum, Wolfram UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoefler, Gerald UNSPECIFIED UNSPECIFIED UNSPECIFIED Dietel, Manfred UNSPECIFIED UNSPECIFIED UNSPECIFIED Weichert, Wilko UNSPECIFIED UNSPECIFIED UNSPECIFIED Schirmacher, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-273211
DOI:	10.1007/s00428-016-1919-8
Journal or Publication Title:	Virchows Arch.
Volume:	468
Number:	6
Page Range:	S. 697 - 706
Date:	2016
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-2307
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HEREDITARY BREAST; PATHOGENESIS; PATTERNS; THERAPY Multiple languages Pathology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27321