Klinische Anwendungsbeispiele einer Next-Generation-Sequencing-basierten Multi-Genpanel-Analyse

Zusammenfassung

Dieser Übersichtsartikel bietet einen Überblick über klinisch sinnvolle Anwendungsgebiete einer Next-Generation-Sequencing-basierten (NGS) Multi-Genpanel-Teststrategie in den Bereichen Onkologie, hereditärer Tumorsyndrome und Hämatologie. Bei soliden Tumoren (z.B. Lungenkarzinom, Kolonrektalkarzinom) trägt die Detektion somatischer Mutationen nicht nur zu einer besseren diagnostischen, sondern auch therapeutischen Stratifizierung der Betroffenen bei. Die zunehmende genetische Komplexität hereditärer Tumorsyndrome (z.B. Brust- und Ovarialkarzinom, Lynchsyndrom/Polypose) erfordert in betroffenen Familien eine Multi-Genpanel-Analyse von Keimbahnmutationen. Ein weiteres sinnvolles Indikationsgebiet einer Multi-Genpanel-Diagnostik und Prognoseabschätzung sind akute und chronische myeloische Erkrankungen. Die Kriterien der WHO-Klassifikation und des „European LeukemiaNet“-Prognosesystems der akuten myeloischen Leukämie können nur durch eine Multi-Genpanel-Teststrategie erfüllt werden.

Abstract

This review provides an overview of clinically useful applications of a next-generation sequencing (NGS)-based multi-gene panel testing strategy in the areas of oncology, hereditary tumor syndromes, and hematology. In the case of solid tumors (e.g. lung carcinoma, colon-rectal carcinoma), the detection of somatic mutations contributes not only to a better diagnostic but also therapeutic stratification of those affected. The increasing genetic complexity of hereditary tumor syndromes (e.g. breast and ovarian carcinoma, lynch syndrome/polyposis) requires a multi-gene panel analysis of germline mutations in affected families. Another useful indication for a multi-gene panel diagnostics and prognosis assessment are acute and chronic myeloid diseases. The criteria of the WHO-classification and the European LeukemiaNet-prognosis system for acute myeloid leukemia can only be met by a multi-gene panel test strategy.

Kernaussagen

• Eine zielgerichtete, NGS-basierte (Next Generation Sequencing) Multi-Genpanel-Analyse mit der Selektion von klinisch relevanten Genen kann sinnvoll in der Onkologie, bei hereditären Tumorsyndromen und bei hämatologischen Grunderkrankungen eingesetzt werden.

• Kommerziell erhältliche und für den Anwender maßgeschneiderte NGS-Panels ermöglichen bei soliden Tumoren (z.B. Lungenkarzinomen, gastrointestinalen Tumoren) eine exakte Identifizierung von somatischen Mutationen und tragen damit zu einer besseren prognostischen und therapeutischen Einschätzung der Grunderkrankung bei.

• Die differenzialdiagnostische Abklärung von Keimbahnmutationen bei genetisch zunehmend komplexeren, angeborenen Tumorsyndromen (z.B. hereditäres Brust- und Ovarialkarzinom-Syndrom, Lynch-Syndrom und Polypose) durch eine NGS-basierte Multi-Panel-Diagnostik hat sich in der Routinediagnostik bewährt.

• Der Einsatz der NGS-Multi-Genpanel-Analyse im Bereich der Hämatologie (z.B. bei akuten und myeloischen Erkrankungen) ermöglicht eine diagnostische, prognostische und in Verlaufskontrollen detektierbare Veränderung des molekulargenetischen Profils der jeweiligen Grunderkrankung.

Schlüsselwörter

Next-Generation-Sequencing - Multi-Genpanel - Onkologie - hereditäre Tumorsyndrome - Hämatologie

Keywords

Next-generation sequencing - targeted sequencing - oncology - hereditary tumor syndromes - hematology

Publikationsverlauf

Artikel online veröffentlicht:
31. Juli 2023

• Literatur

• 1 Schaflinger E, Enko D. The Impact of Next-Generation Sequencing on Medical Genetic Diagnostics and Counseling. Dtsch Med Wochenschr 2022; 147: 1336-1341
• 2 Nagahashi M, Shimada Y, Ichikawa H. et al. Next generation sequencing-based gene panel tests for the management of solid tumors. Cancer Sci 2019; 110: 6-15
• 3 Lee A, Lee SH, Jung CK. et al. Use of the Ion AmpliSeq Cancer Hotspot Panel in clinical molecular pathology laboratories for analysis of solid tumours: With emphasis on validation with relevant single molecular pathology tests and the Oncomine Focus Assay. Pathol Res Pract 2018; 214: 713-719
• 4 de Biase D, Acquaviva G, Visani M. et al. Molecular Diagnostic of Solid Tumor Using a Next Generation Sequencing Custom-Designed Multi-Gene Panel. Diagnostics (Basel) 2020; 10
• 5 Mosele F, Remon J, Mateo J. et al. Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group. Ann Oncol 2020; 31: 1491-1505
• 6 Teixeira MR, Oliveira J, Borralho P. et al. Portuguese Consensus Recommendations for Next-Generation Sequencing of Lung Cancer, Rare Tumors, and Cancers of Unknown Primary Origin in Clinical Practice. Acta Med Port 2022;
• 7 Yatabe Y, Sunami K, Goto K. et al. Multiplex gene-panel testing for lung cancer patients. Pathol Int 2020; 70: 921-931
• 8 Penault-Llorca F, Kerr KM, Garrido P. et al. Expert opinion on NSCLC small specimen biomarker testing – Part 2: Analysis, reporting, and quality assessment. Virchows Arch 2022;
• 9 Bregni G, Sticca T, Camera S. et al. Feasibility and clinical impact of routine molecular testing of gastrointestinal cancers at a tertiary centre with a multi-gene, tumor-agnostic, next generation sequencing panel. Acta Oncol 2020; 59: 1438-1446
• 10 Moorcraft SY, Gonzalez de Castro D, Cunningham D. et al. Investigating the feasibility of tumour molecular profiling in gastrointestinal malignancies in routine clinical practice. Ann Oncol 2018; 29: 230-236
• 11 Mukherji R, Yin C, Hameed R. et al. The current state of molecular profiling in gastrointestinal malignancies. Biol Direct 2022; 17: 15
• 12 de Biase D, Malapelle U, De Leo A. et al. Multi-gene custom panels for the characterisation of metastatic colorectal carcinoma in clinical practice: express the role of PIK3CA mutations. J Clin Pathol 2022; 75: 488-492
• 13 Chevrier S, Brasselet A, Carnet M. et al. Custom multitumor nextgeneration sequencing panel for routine molecular diagnosis of solid tumors: Validation and results from threeyear clinical use. Int J Mol Med 2022; 49
• 14 Perne C, Steinke-Lange V, Aretz S. et al. Rare tumors as leading symptom of hereditary tumor syndromes. Pathologe 2020; 41: 535-549
• 15 Ramirez-Calvo M, Garcia-Casado Z, Fernandez-Serra A. et al. Implementation of massive sequencing in the genetic diagnosis of hereditary cancer syndromes: diagnostic performance in the Hereditary Cancer Programme of the Valencia Community (FamCan-NGS). Hered Cancer Clin Pract 2019; 17: 3
• 16 Paduano F, Colao E, Fabiani F. et al. Germline Testing in a Cohort of Patients at High Risk of Hereditary Cancer Predisposition Syndromes: First Two-Year Results from South Italy. Genes (Basel) 2022; 13
• 17 Kamps R, Brandao RD, Bosch BJ. et al. Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification. Int J Mol Sci 2017; 18
• 18 Gaspersic J, Videtic Paska A. Potential of modern circulating cell-free DNA diagnostic tools for detection of specific tumour cells in clinical practice. Biochem Med (Zagreb) 2020; 30: 030504
• 19 Shinriki S, Maeshiro M, Shimamura K. et al. Evaluation of an amplicon-based custom gene panel for the diagnosis of hereditary tumors. Neoplasma 2020; 67: 898-908
• 20 Green RC, Berg JS, Grody WW. et al. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med 2013; 15: 565-574
• 21 Taylor A, Brady AF, Frayling IM. et al. Consensus for genes to be included on cancer panel tests offered by UK genetics services: guidelines of the UK Cancer Genetics Group. J Med Genet 2018; 55: 372-377
• 22 Manahan ER, Kuerer HM, Sebastian M. et al. Consensus Guidelines on Genetic` Testing for Hereditary Breast Cancer from the American Society of Breast Surgeons. Ann Surg Oncol 2019; 26: 3025-3031
• 23 Tsaousis GN, Papadopoulou E, Agiannitopoulos K. et al. Revisiting the Implications of Positive Germline Testing Results Using Multi-gene Panels in Breast Cancer Patients. Cancer Genomics Proteomics 2022; 19: 60-78
• 24 Castillo-Guardiola V, Rosado-Jimenez L, Sarabia-Meseguer MD. et al. Next step in molecular genetics of hereditary breast/ovarian cancer: Multigene panel testing in clinical actionably genes and prioritization algorithms in the study of variants of uncertain significance. Eur J Med Genet 2022; 65: 104468
• 25 Angeli D, Salvi S, Tedaldi G. Genetic Predisposition to Breast and Ovarian Cancers: How Many and Which Genes to Test?. Int J Mol Sci 2020; 21
• 26 Shin HC, Lee HB, Yoo TK. et al. Detection of Germline Mutations in Breast Cancer Patients with Clinical Features of Hereditary Cancer Syndrome Using a Multi-Gene Panel Test. Cancer Res Treat 2020; 52: 697-713
• 27 Guglielmi C, Scarpitta R, Gambino G. et al. Detection of Germline Variants in 450 Breast/Ovarian Cancer Families with a Multi-Gene Panel Including Coding and Regulatory Regions. Int J Mol Sci 2021; 22
• 28 Mao R, Krautscheid P, Graham RP. et al. Genetic testing for inherited colorectal cancer and polyposis, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG). Genet Med 2021; 23: 1807-1817
• 29 Stern B, McGarrity T, Baker M. Incorporating Colorectal Cancer Genetic Risk Assessment into Gastroenterology Practice. Curr Treat Options Gastroenterol 2019; 17: 702-715
• 30 Rohlin A, Rambech E, Kvist A. et al. Expanding the genotype-phenotype spectrum in hereditary colorectal cancer by gene panel testing. Fam Cancer 2017; 16: 195-203
• 31 Tanakaya K. Current clinical topics of Lynch syndrome. Int J Clin Oncol 2019; 24: 1013-1019
• 32 Kraft IL, Godley LA. Identifying potential germline variants from sequencing hematopoietic malignancies. Blood 2020; 136: 2498-2506
• 33 Ferrone CK, Wong H, Semenuk L. et al. Validation, Implementation, and Clinical Impact of the Oncomine Myeloid Targeted-Amplicon DNA and RNA Ion Semiconductor Sequencing Assay. J Mol Diagn 2021; 23: 1292-1305
• 34 Khoury JD, Solary E, Abla O. et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia 2022; 36: 1703-1719
• 35 DiNardo CD, Cortes JE. Mutations in AML: prognostic and therapeutic implications. Hematology Am Soc Hematol Educ Program 2016; 2016: 348-355
• 36 Dohner H, Estey E, Grimwade D. et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 2017; 129: 424-447
• 37 Bhai P, Hsia CC, Schenkel LC. et al. Clinical Utility of Implementing a Frontline NGS-Based DNA and RNA Fusion Panel Test for Patients with Suspected Myeloid Malignancies. Mol Diagn Ther 2022; 26: 333-343
• 38 Gargallo P, Molero M, Bilbao C. et al. Next-Generation DNA Sequencing-Based Gene Panel for Diagnosis and Genetic Risk Stratification in Onco-Hematology. Cancers (Basel) 2022; 14
• 39 Dohner H, Wei AH, Appelbaum FR. et al. Diagnosis and Management of AML in Adults: 2022 ELN Recommendations from an International Expert Panel. Blood 2022;
• 40 Sargas C, Ayala R, Chillon MC. et al. Networking for advanced molecular diagnosis in acute myeloid leukemia patients is possible: the PETHEMA NGS-AML project. Haematologica 2021; 106: 3079-3089
• 41 Haferlach T. Advancing leukemia diagnostics: Role of Next Generation Sequencing (NGS) in acute myeloid leukemia. Hematol Rep 2020; 12: 8957