Objectives
  • To be able to describe how genomics might improve the understanding and management of patients with cancer, within a frame of coordinated clinical case, interacting with pathologists and clinical geneticists for adequate analytical and postanalytical interpretation of results

  • To be able to accurately assess the clinical validity and clinical utility of genomic variants and technologies

  • To be able to critically appraise new genomic technologies taking into account the downstream costs secondary to genomic analysis for the laboratory and the patient, including the costs associated with new technologies

Awareness
  • Awareness of the key metrics and parameters that govern projects involving molecular pathology techniques such as next-generation sequencing (NGS), with an awareness of the differences in detection limit of the assays, the limitations of the different assays and the importance of pre-analytical variables on the results

  • Appreciation that some molecular pathology technologies—for example, gene expression profiling (GEP) and multigene cancer panels—may not give absolute, binary results, rather than they may lead to results that are equivocal in terms of classification, and indeed even to results with uncertain clinical validity and utility

  • Recognition of the importance of current and future applications in clinical practice of any molecular pathology technology, such as NGS, being aware of the need to have uniformity in planning genomic single versus multiplex testing only when there is a clear purpose and clinical need, with an appropriate use of multigene panels and full integration with all clinicopathological variables, participation and discussion within established expert Molecular Advisory Boards, and with disclosure of results according to established levels of evidence

  • Awareness of the distinction between established clinical variants versus promising variants in genomics, being aware that the importance of these variants may change in time, being aware of potential false calls of non-validated variants with no clinical utility, with a need to have an evidence-based approach to germline variants encountered in somatic mutation profiling

  • Appreciation of the need to discuss with patients the implications of genomic testing and of direct-to-consumer test marketing for patients, including awareness of the importance of interaction with general practitioners on genomic testing, informed consent and pre-test counselling, access to genetic services whenever applicable, disclosure of genomic information of uncertain significance, message framing and understanding the limitations of patients’ knowledge on the concepts and goals of precision medicine

  • Appreciation of the importance of appropriate regulatory endorsement and regulation for somatic and germline genomic testing, with awareness of the costs of the assay and the often limited or unavailable funding for the assay within most healthcare systems

  • Awareness of the need of oncology providers to communicate the potential for incidental and secondary germline information to patients before conducting somatic mutation profiling, with an assessment on the potential benefits, limitations and risks before testing

  • Awareness that there are different types of assays that can be used in a laboratory, namely regulatory-approved assays, laboratory-developed assays with internal evidence for analytical validity and purely research assays

  • Awareness that different assays do provide different types of information, namely diagnostic, prognostic and/or predictive information

Knowledge
  • Knowledge about the main clinical diagnostic test modalities, namely cytogenetics, flow cytometry, immunohistochemistry (IHC), fluorescence in situ hybridisation (FISH), reverse transcriptase polymerase chain reaction (RT-PCR), Sanger sequencing, microarrays (eg, single-nucleotide polymorphism (SNP) chips) and NGS

  • Knowledge on the interpretation of genomic information of whatever kind (FISH, PCR, multiplex ligation-dependent probe amplification (MLPA), mass spectrometry analysis (MSA), array comparative genomic hybridisation (aCGH), array SNP (aSNP), NGS, GEP etc) in association with personal medical and health information

  • Knowledge of the standards of scientific genomic and clinical evidence for all types of assays (FISH, PCR, NGS etc)

  • Knowledge on the current and near-future diagnostic applications of NGS

  • Knowledge that within NGS there is a conceptual distinction between panel sequencing, exome sequencing and genome-wide sequencing

  • Knowledge on the interpretation of key metrics and parameters that govern projects involving molecular pathology, especially when NGS is being used

  • Knowledge on how to ascertain patient preferences regarding the receipt of germline information and assessment on how to allow patients to decline receiving of germline information

  • Knowledge on how to apply basic concepts of cancer genetics, risk assessment and currently available testing into patient care practices

  • Knowledge on how to recognise genetic testing for common cancer syndromes and how to interpret variants of unknown significance (VUS)

  • Knowledge on the basic laboratory-specific concepts, the laboratory sample flow, different turn-around times for different molecular pathology techniques and understanding of the limitations of data generation using high throughput technologies such as NGS

  • Knowledge on the emergent strategies and the latest advances using molecular pathology techniques such as NGS in the early detection of cancers (breast, gastrointestinal etc)

  • Knowledge on the patient's perspective on preferences for somatic testing, the importance of costs of the assay for the patient and the potential need of return of results when multiparameter testing is performed

  • Knowledge on the basic physiological and pathophysiological mechanisms of normal and diseased tissues, for example the immune system, DNA-repair mechanisms etc

Skills
  • Ability to distinguish between established clinical variants versus promising variants in genomics

  • Ability to adequately assess the clinical validity and clinical utility of genomic variants and technologies

  • Ability to identify whether an assay is directed to DNA, RNA or protein

  • Ability to identify the concept the assay is based on, namely either testing for a specific analyte, a panel test that is used for multiple analytes or an open, so-called unbiased, genome-wide assay

  • Ability to recognise when the molecular result is considered the most important and definitive finding, as opposed to being just one piece of information that goes into determination of: diagnosis (where it is subordinate to haematoxylin & eosin (H&E) histology); prognosis (where it is subordinate to or may have to be integrated with other staging information); and prediction (where expression of a drug's target does not necessarily mean that the drug will work and provide clinical response or clinical benefit)

  • Ability to identify that different molecular changes are relevant in different clinical situations: point mutations, copy number aberrations, translocations, gene expression levels and protein levels, and that these need different types of samples that are tested using different techniques