TY - JOUR
T1 - Evaluation of a Hybrid Capture–Based Pan-Cancer Panel for Analysis of Treatment Stratifying Oncogenic Aberrations and Processes
AU - Kroeze, Leonie I.
AU - de Voer, Richarda M.
AU - Kamping, Eveline J.
AU - von Rhein, Daniel
AU - Jansen, Erik A.M.
AU - Hermsen, Mandy J.W.
AU - Barberis, Massimo C.P.
AU - Botling, Johan
AU - Garrido-Martin, Eva M.
AU - Haller, Florian
AU - Lacroix, Ludovic
AU - Maes, Brigitte
AU - Merkelbach-Bruse, Sabine
AU - Pestinger, Valerie
AU - Pfarr, Nicole
AU - Stenzinger, Albrecht
AU - van den Heuvel, Michel M.
AU - Grünberg, Katrien
AU - Ligtenberg, Marjolijn J.L.
N1 - Publisher Copyright:
© 2020 Association for Molecular Pathology and American Society for Investigative Pathology
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85085281758&partnerID=8YFLogxK
U2 - 10.1016/j.jmoldx.2020.02.009
DO - 10.1016/j.jmoldx.2020.02.009
M3 - Article
C2 - 32205293
AN - SCOPUS:85085281758
SN - 1525-1578
VL - 22
SP - 757
EP - 769
JO - Journal of Molecular Diagnostics
JF - Journal of Molecular Diagnostics
IS - 6
ER -