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4 results on '"Tops, Bastiaan B J"'

1. Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material.

Author

Steeghs EMP, Kroeze LI, Tops BBJ, van Kempen LC, Ter Elst A, Kastner-van Raaij AWM, Hendriks-Cornelissen SJB, Hermsen MJW, Jansen EAM, Nederlof PM, Schuuring E, Ligtenberg MJL, and Eijkelenboom A

Subjects
Colorectal Neoplasms diagnosis, Colorectal Neoplasms genetics, Female, Gastrointestinal Stromal Tumors diagnosis, Gastrointestinal Stromal Tumors genetics, Gene Amplification, High-Throughput Nucleotide Sequencing methods, Humans, Lung Neoplasms diagnosis, Lung Neoplasms genetics, Male, Melanoma diagnosis, Melanoma genetics, Microsatellite Instability, Neoplasms diagnosis, Early Detection of Cancer methods, Mutation, Neoplasm Proteins genetics, Neoplasms genetics, Sequence Analysis, DNA methods
Abstract

Background: Sensitive and reliable molecular diagnostics is needed to guide therapeutic decisions for cancer patients. Although less material becomes available for testing, genetic markers are rapidly expanding. Simultaneous detection of predictive markers, including mutations, gene amplifications and MSI, will save valuable material, time and costs., Methods: Using a single-molecule molecular inversion probe (smMIP)-based targeted next-generation sequencing (NGS) approach, we developed an NGS panel allowing detection of predictive mutations in 33 genes, gene amplifications of 13 genes and microsatellite instability (MSI) by the evaluation of 55 microsatellite markers. The panel was designed to target all clinically relevant single and multiple nucleotide mutations in routinely available lung cancer, colorectal cancer, melanoma, and gastro-intestinal stromal tumor samples, but is useful for a broader set of tumor types., Results: The smMIP-based NGS panel was successfully validated and cut-off values were established for reliable gene amplification analysis (i.e. relative coverage ≥3) and MSI detection (≥30% unstable loci). After validation, 728 routine diagnostic tumor samples including a broad range of tumor types were sequenced with sufficient sensitivity (2.4% drop-out), including samples with low DNA input (< 10 ng; 88% successful), low tumor purity (5-10%; 77% successful), and cytological material (90% successful). 75% of these tumor samples showed ≥1 (likely) pathogenic mutation, including targetable mutations (e.g. EGFR, BRAF, MET, ERBB2, KIT, PDGFRA). Amplifications were observed in 5.5% of the samples, comprising clinically relevant amplifications (e.g. MET, ERBB2, FGFR1). 1.5% of the tumor samples were classified as MSI-high, including both MSI-prone and non-MSI-prone tumors., Conclusions: We developed a comprehensive workflow for predictive analysis of diagnostic tumor samples. The smMIP-based NGS analysis was shown suitable for limited amounts of histological and cytological material. As smMIP technology allows easy adaptation of panels, this approach can comply with the rapidly expanding molecular markers.

Published
2020
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2. Mutational analysis using Sanger and next generation sequencing in sporadic spindle cell hemangiomas: A study of 19 cases.

Author

Ten Broek RW, Bekers EM, de Leng WWJ, Strengman E, Tops BBJ, Kutzner H, Leeuwis JW, van Gorp JM, Creytens DH, Mentzel T, van Diest PJ, Eijkelenboom A, and Flucke U

Subjects
Adolescent, Adult, Aged, Child, Female, Hemangioma pathology, Humans, Isocitrate Dehydrogenase genetics, Male, Middle Aged, Soft Tissue Neoplasms pathology, Hemangioma genetics, Mutation, Soft Tissue Neoplasms genetics
Abstract

Spindle cell hemangioma (SCH) is a distinct vascular soft-tissue lesion characterized by cavernous blood vessels and a spindle cell component mainly occurring in the distal extremities of young adults. The majority of cases harbor heterozygous mutations in IDH1/2 sporadically or rarely in association with Maffucci syndrome. However, based on mosaicism and accordingly a low percentage of lesional cells harboring a mutant allele, detection can be challenging. We tested 19 sporadic SCHs by Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), conventional next generation sequencing (NGS), and NGS using a single molecule molecular inversion probes (smMIP)-based library preparation to compare their diagnostic value. Out of 10 cases tested by Sanger sequencing and 2 analyzed using MLPA, 4 and 1, respectively, revealed a mutation in IDH1 (p.R132C). The 7 remaining negative cases and additional 6 cases were investigated using smMIP/NGS, showing hot spot mutations in IDH1 (p.R132C) (8 cases) and IDH2 (3 cases; twice p.R172S and once p.R172G, respectively). One case was negative. Owing to insufficient DNA quality and insufficient coverage, 2 cases were excluded. In total, in 16 out of 17 cases successfully tested, an IDH1/2 mutation was found. Given that IDH1/2 mutations were absent in 161 other vascular lesions tested by smMIP/NGS, the mutation can be considered as highly specific for SCH., (© 2017 Wiley Periodicals, Inc.)

Published
2017
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4. RAS testing in metastatic colorectal cancer : Excellent reproducibility amongst 17 Dutch pathology centers

Author

Boleij, Annemarie, Tops, Bastiaan B J, Rombout, Paul D.M., Dequeker, Elizabeth M., Ligtenberg, Marjolijn J. L., van Krieken, J. Han, van Noesel, Carel J M, Scheidel-Jacobse, Karen C., Kummer, J. A., Roepman, P., Prinsen, C.F.M., van den Berg-van Erp, S. H.M., van Gorp, J. M.H.H., Nederlof, Petra M., Caspers, E., Dinjens, Winand N M, Beerens, E. C.W., 't Hart, N. A., van den Brule, Adriaan J. C., van der Geize, R., Riemersma, S. A., van Wezel, T., Morreau, H., van Eijk, R., Jeuken, J. W.M., Dirkx, A., Klomp, J.M., van Blokland, W. T.M., ter Elst, A., Schuuring, E., Diepstra, A., Heideman, Danielle A. M., van Grieken, Nicole C. T., Sie, D., Targeted Gynaecologic Oncology (TARGON), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Stem Cell Aging Leukemia and Lymphoma (SALL), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
Neuroblastoma RAS viral oncogene homolog, Pathology, Colorectal cancer, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], WILD-TYPE KRAS, THERAPY, GTP Phosphohydrolases, Metastasis, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Medicine, University medical, Netherlands, Molecular pathology, Antibodies, Monoclonal, High-Throughput Nucleotide Sequencing, CETUXIMAB, ErbB Receptors, Oncology, TRIAL, Colorectal Neoplasms, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, Antineoplastic Agents, Primary care, Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9], Reference laboratory, ASSURANCE, PANITUMUMAB, Proto-Oncogene Proteins p21(ras), PERCENTAGE, Next generation sequencing, External quality assessment, Humans, Genetic Testing, EXTERNAL-QUALITY-ASSESSMENT, Base Sequence, business.industry, MUTATIONS, Membrane Proteins, Quality control, Sequence Analysis, DNA, medicine.disease, digestive system diseases, Mutation, RAS Mutation, CELLS, Clinical Research Paper, business, RAS
Abstract

// Annemarie Boleij 1 , Bastiaan B.J. Tops 2 , Paul D.M. Rombout 1 , Elizabeth M. Dequeker 3 , Marjolijn J.L. Ligtenberg 1,2 , J. Han van Krieken 1 and Dutch RAS EQA Initiative 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20 1 Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands 2 Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands 3 Department of Public Health and Primary Care, Biomedical Quality Assurance Research Unit, KU Leuven - University of Leuven, Leuven, Belgium 4 C.J.M. van Noesel, Academic Medical Center (AMC), Department of Pathology, Amsterdam 5 C.C. Scheidel-Jacobse (Technical specialist), J.A. Kummer (Pathologist/KMBP), P. Roepman (KMBP in training), St. Antonius Ziekenhuis, Department of Pathology, Nieuwegein 6 C.F.M. Prinsen (KMBP), S.H.M. van den Berg-van Erp (Pathologist), Canisius Wilhelmina Ziekenhuis (CWZ), Department of Pathology, Nijmegen 7 J.M.H.H. van Gorp, Diakonessenhuis, Laboratory for Pathology, Utrecht 8 P.M. Nederlof, Dutch Cancer Institute (NKI), Amsterdam. 9 E. Caspers, St. Elisabeth Ziekenhuis, Department of Molecular Pathology, Tilburg 10 W.N.M. Dinjens, E.C.W. Beerens, Erasmus MC, Department of Pathology, Molecular Diagnostics, Rotterdam 11 N.A. ‘t Hart, Isala, Department of Pathology, Zwolle 12 A.J.C. van den Brule, Jeroen Bosch Ziekenhuis, Molecular Diagnostics, ‘s-Hertogenbosch 13 R. van der Geize (KMBP), S.A. Riemersma (Pathologist), Laboratory for Pathology Oost-Nederland (LABPON), Hengelo 14 T. van Wezel (KMBP), H. Morreau (Pathologist), R. van Eijk (Technical specialist), Leiden University Medical Center (LUMC), Department of Pathology, Leiden 15 J.W.M. Jeuken, Laboratory for Pathology and Medical Microbiology (PAMM), Eindhoven 16 A. Dirkx, Pathan B.V., Molecular Diagnostics, Rotterdam 17 M. Klomp, Rijnstate Ziekenhuis, Department of Pathology, Arnhem 18 W.T.M van Blokland, University Medical Center (UMC) Utrecht, Molecular Pathology, Utrecht 19 A. ter Elst (Technical specialist/KMBP in training), E. Schuuring (KMBP), A. Diepstra (Pathologist), University Medical Center Groningen (UMCG), Department of Pathology, Groningen 20 D.A.M. Heideman (KMBP), N.C.T. van Grieken (Pathologist), D. Sie (Technical specialist), VU-University Medical Center (VUMC), Department of Pathology, Amsterdam Correspondence to: J.Han van Krieken, email: // Keywords : RAS, colorectal cancer, metastasis, quality control, next generation sequencing Received : February 09, 2015 Accepted : March 18, 2015 Published : April 12, 2015 Abstract In 2013 the European Medicine Agency (EMA) restricted the indication for anti-EGFR targeted therapy to metastatic colorectal cancer (mCRC) with a wild-type RAS gene, increasing the need for reliable RAS mutation testing. We evaluated the completeness and reproducibility of RAS -testing in the Netherlands. From 17 laboratories, tumor DNA of the first 10 CRC cases tested in 2014 in routine clinical practice was re-tested by a reference laboratory using a custom next generation sequencing panel. In total, 171 CRC cases were re-evaluated for hotspot mutations in KRAS , NRAS and BRAF . Most laboratories had introduced complete RAS -testing (65%) and BRAF -testing (71%) by January 2014. The most employed method for all hotspot regions was Sanger sequencing (range 35.7 – 49.2%). The reference laboratory detected all mutations that had been found in the participating laboratories ( n = 92), plus 10 additional mutations. This concerned three RAS and seven BRAF mutations that were missed due to incomplete testing of the participating laboratory. Overall, the concordance of tests performed by both the reference and participating laboratory was 100% (163/163; κ-static 1.0) for RAS and 100% (144/144; κ-static 1.0) for BRAF . Our study shows that RAS and BRAF mutations can be reproducibly assessed using a variety of testing methods.

Published
2015

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