Objectives	To describe and communicate basic test performance, including knowledge of the underlying technology and methodology and appropriate fields of application To be able to accurately assess the clinical validity and clinical utility of genetic test results, appropriately discuss results with patients, and effectively communicate as part of a multidisciplinary team (eg, pathologists, clinical geneticists, and other stakeholders in a molecular tumour board)
Key Concepts	Recognise that there are legal, ethical, and social implications of genetic testing Demonstrate an understanding for the patient's perspective (including preferences for testing, costs of the assay for the patient, and the potential need for additional follow-up testing or counselling) Distinguish among the different types of genomic assays that can be used in a laboratory: regulatory-approved assays, laboratory-developed assays, and research use only tests Distinguish among the diagnostic, prognostic, and/or predictive information that genomic tests may contain Determine the best approach for obtaining genetic data (eg, tissue and body fluids including blood such as liquid biopsy) Distinguish each test method and genomic test including test parameters (eg, sensitivity, specificity, accuracy, precision, and positive and negative predictive value) Classify genomic tests into next-generation sequencing (NGS) v non-NGS assays (non-NGS include in situ assays and single gene testing, such as different types of polymerase chain reaction [PCR]-based assays and Sanger sequencing) Recognise that NGS-based test can be differentiated according to their genomic coverage, ranging from small gene panels (usually covering hotspot regions of 20-50 major cancer genes) to large gene panels (around ≥1 Megabase genomic footprint) and whole exome (WES) as well as whole genome sequencing (WGS) Describe the approaches to NGS testing. With the exception of whole genome sequencing, target enrichment methods are used. Main methods are: hybrid capture, AmpliSeq, anchored multiplex PCR, and single primer extension Classify tissue-based genomic tests as tumour-only sequencing v parallel sequencing of the tumour and germline DNA (usually obtained from lymphocytic DNA in a blood draw) Recognise that tumour-only sequencing harbours genetic information from both somatic and germline DNA. Further work-up may be required if there are possible germline variants detected (eg, confirmatory germline testing and genetic counselling). For whole exome and whole genome sequencing (WES/WGS), parallel germline sequencing is critical Recognise that using NGS, gene fusions can be interrogated at both the DNA (break points) and RNA (transcripts) level. Parallel analysis is ideal. For formalin-fixed and paraffin embedded (FFPE), RNA sequencing is preferred over DNA sequencing Recognise that in contrast to fresh tissue, FFPE material harbours deamination artifacts (C>T transitions) that need to be accounted for in the analysis and influence sensitivity of test results Recognise that liquid biopsies are based on the analysis of the tumour DNA containing fraction of cell-free DNA. Sensitivity is particularly influenced by the number of nucleic acid molecules per locus and the sequencing depth/sensitivity per locus Explain the common pre-analytic variables that may influence test results and include age of archival material, tumour cellularity, quality and quantity of nucleic acids, as well as conditions for collection, preparation, transport, and storage of sample and analyte types Recognise that post-analytic variables in NGS-based testing primarily include bioinformatic tools and filters used for data processing including variant calling, annotation, functional, and clinical variant interpretation
Skills	Demonstrate the ability to: Present core definitions and terms of genomic testing Present core knowledge of genetic testing technology and methodology Identify whether an assay is directed to DNA, RNA, or protein (eg, methylation analysis, whole exome sequencing, transcriptome sequencing, proteome analysis including IHC) Identify the concept the assay is based on, namely either testing for a specific analyte, a panel test, ie, used for multiple analytes or an open, so-called, unbiased, genome-wide assay Recognise different genomic aberrations and methods of detection: missense, nonsense, frameshift mutations, indels, copy number aberrations, translocations/gene fusions, gene expression/transcript levels, and protein levels Classify and interpret genomic variants according to established classification systems and interpret variants in their proper clinical contexts Discuss the clinical indications for molecular testing in oncology, including applications in screening, diagnosis, prognosis, response prediction, disease and treatment monitoring, identification of resistance mechanisms, and evaluation for inherited conditions Apply genetic counselling principles, including communicating to family members in need of further testing, and preparing patients for the potential for incidental and secondary germline information before conducting somatic mutation profiling