Universität zu Köln

Kroeze, Leonie I., de Voer, Richarda M., Kamping, Eveline J., von Rhein, Daniel, Jansen, Erik A. M., Hermsen, Mandy J. W., Barberis, Massimo C. P., Botling, Johan, Garrido-Martin, Eva M., Haller, Florian, Lacroix, Ludovic, Maes, Brigitte, Merkelbach-Bruse, Sabine, Pestinger, Valerie, Pfarr, Nicole, Stenzinger, Albrecht, van den Heuvel, Michel M., Grunberg, Katrien and Ligtenberg, Marjolijn J. L. (2020). Evaluation of a Hybrid Capture-Based Pan-Cancer Panel for Analysis of Treatment Stratifying Oncogenic Aberrations and Processes. J. Mol. Diagn., 22 (6). S. 757 - 770. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1943-7811

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Abstract

Stratification of patients for targeted and immune-based therapies requires extensive genomic profiling that enables sensitive detection of clinically relevant variants and interrogation of biomarkers, such as tumor mutational burden (TMB) and microsatellite instability (MSI). Detection of single and multiple nucleotide variants, copy number variants, MSI, and TMB was evaluated using a commercially available next-generation sequencing panel containing 523 cancer-related genes (1.94 megabases). Analysis of formalin-fixed, paraffin-embedded tissue sections and cytologic material from 45 tumor samples showed that all previously known MSI-positive samples (n = 7), amplifications (n = 9), and pathogenic variants (n = 59) could be detected. TMB and MSI scores showed high intralaboratory and interlaboratory reproducibility (eight samples tested in 11 laboratories). For reliable TMB analysis, 20 ng DNA was shown to be sufficient, even for relatively poor-quality samples. A minimum of 20% neoplastic cells was required to minimize variations in TMB values induced by chromosomal instability or tumor heterogeneity. Subsequent analysis of 58 consecutive lung cancer samples in a diagnostic setting was successful and revealed sufficient somatic mutations to generate mutational signatures in 14 cases. In conclusion, the 523-gene assay can be applied for evaluation of multiple DNA-based biomarkers relevant for treatment selection.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kroeze, Leonie I. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Voer, Richarda M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kamping, Eveline J. UNSPECIFIED UNSPECIFIED UNSPECIFIED von Rhein, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Jansen, Erik A. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hermsen, Mandy J. W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Barberis, Massimo C. P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Botling, Johan UNSPECIFIED UNSPECIFIED UNSPECIFIED Garrido-Martin, Eva M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Haller, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Lacroix, Ludovic UNSPECIFIED UNSPECIFIED UNSPECIFIED Maes, Brigitte UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkelbach-Bruse, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Pestinger, Valerie UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfarr, Nicole UNSPECIFIED UNSPECIFIED UNSPECIFIED Stenzinger, Albrecht UNSPECIFIED UNSPECIFIED UNSPECIFIED van den Heuvel, Michel M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Grunberg, Katrien UNSPECIFIED UNSPECIFIED UNSPECIFIED Ligtenberg, Marjolijn J. L. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-332047
DOI:	10.1016/j.jmoldx.2020.02.009
Journal or Publication Title:	J. Mol. Diagn.
Volume:	22
Number:	6
Page Range:	S. 757 - 770
Date:	2020
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 TUMOR MUTATIONAL BURDEN; NIVOLUMAB PLUS IPILIMUMAB; MICROSATELLITE INSTABILITY; PD-L1 EXPRESSION; IMMUNOHISTOCHEMISTRY; SIGNATURES; BLOCKADE; EFFICACY Multiple languages Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33204