Solid Tumours 1 (SLS428)

10 credits

Aim of this module

This module provides trainees with an introduction into the molecular mechanisms leading to the development of solid cancer and the associated genomic testing. Using colorectal cancer and melanoma as exemplars throughout, they will understand the organisation and delivery of a diagnostic tumour genotyping service. They will perform some common methods used for diagnostic testing of these cancers and gain an understanding into both the analysis and interpretation of patient results, and the need for additional investigations and the importance of cross-discipline working in both the laboratory and wider clinical setting.

  1. Interact with relevant disciplines for the diagnosis and treatment of cancer patients
  2. Understand the importance of cellularity, necrosis and tumour burden in the context of upstream testing
  3. Apply the appropriate testing strategy for patients referred for diagnostic testing for colorectal cancer and melanoma
  4. Perform the appropriate level of molecular diagnostic testing and monitoring for colorectal cancer and melanoma dependent on histopathological findings
  5. Apply the principles of internal quality control and external quality assessment and draw conclusions about assay performance
  6. Investigate the clinical significance of variants identified using a range of bioinformatics tools following best practice guidelines
  7. Interpret and report clinically relevant findings of the results of laboratory tests
  8. Perform reflex testing for both somatic and germline cancers
Number Work-based learning outcome Title Knowledge
1 1,3

Receive samples and referral information for a range of colorectal cancer and melanoma referrals

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2 2,3

Perform histopathological sample preparation and morphological assessment of neoplastic cells

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3 3,4,5

Select and perform the correct genetic tests(s) for samples from patients referred with colorectal cancer

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4 3,4,5,8

Select and perform the correct genetic tests(s) for samples from patients referred with melanoma

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5 6,7

Use bioinformatics software and associated databases for analysis and interpretation of genomic aberrations in colorectal and melanoma cancer

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6 7,8

Prepare a range of full and accurate interpretative clinical reports for patients referred with colorectal cancer and melanoma.

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7 1,7

Assist with the preparation of cases to be discussed and reviewed in an MDT meeting with other healthcare professionals

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You must complete
2 Case-based discussion(s)
2 of the following DOPS / OCEs
Assessment Title Type
Perform basic morphological assessment demonstrating awareness of neoplastic cells, cellularity, necrosis and tumour material DOPS
Perform DNA extraction of suitable samples types which may include but are not limited to FFPE, fresh tumour and blood DOPS
Perform tumour genotype analysis using bioinformatic pipelines and associated tools DOPS
Produce a diagnostic clinical report for a patient with hotspot mutation(s) DOPS
Discuss patient results with a healthcare professional telephone or in person OCE
Discuss implications of receiving an unlabeled sample with a healthcare professional. OCE
Participate in an MDT meeting with other healthcare professionals OCE
Prepare a clinical report DOPS

Important information

The academic parts of this module will be detailed and communicated to you by your university. Please contact them if you have questions regarding this module and its assessments. The module titles in your MSc may not be exactly identical to the work-based modules shown in the e-portfolio. Your modules will be aligned, however, to ensure that your academic and work-based learning are complimentary.

Learning Outcomes

  1. Understand the aetiology and biological processes leading to cancer development
  2. Describe the genetic mechanisms underpinning the development of cancer
  3. Summarise the appropriate testing strategy dependent on disease status and other test results
  4. Explain the appropriate technologies and their application to the analysis of the disease, to include reflex testing
  5. Describe the patient pathway from sampling to reporting of laboratory findings, including integrated reporting and feedback of results
  6. Evaluate the appropriate therapeutics, inhibitors or other appropriate therapies to guide patient disease management depending on the clinical status such as metastases and genomic results

Indicative Content

Basic principles of molecular biology

  • Oncogenes and tumour suppressor genes
  • Driver and passenger mutations

 Pathogenesis of colorectal and melanoma cancer

  • Aetiology
  • Molecular basis and underlying mechanisms, including epigenetics
  • Driver and passenger mutations
  • Signalling pathways and associated genes
  • Mechanisms of genomic aberrations in colorectal and melanoma cancer
  • Associated genomic aberrations and role within diagnosis and disease management
  • Current Nomenclature used to describe genomic alterations
  • Metatstasis, relaspse
  • Germline associations

 Design, Operation and Performance of technologies used to investigate genomic diseases

  • Current laboratory techniques and methodologies employed for tumour genotyping (e.g. extraction, polymerase chain reaction, sequencing technologies)
    • bespoke assays/in-house
    • commercially available kits
  • Histopathological sample processing requirements for genotyping and impact on upstream testing
    • Impact of fixation on nucleic acid integrity
    • Neoplastic cell content
    • Necrosis
    • Cellularity
    • Macrodissection
  • Nucleic acid extraction methodologies
  • Analytical and Clinical sensitivity and Specificity of these tests, including limits of detection (LOD)
    • Understanding the significance of low level variants in the clinical context
  • The use of bioinformatics tools and relevant genomic databases
  • Quality control, validation and verification, external quality assessment schemes
  • Accurate clinical report writing
  • Standardisation and the use of appropriate tools and nomenclature for reporting variants
  • Potential application of relevant emerging technologies (e.g. Digital pathology)

 Therapeutics

  • Genomic aberrations seen in colorectal and melanoma cancer and their role in disease management in the context of their predictive and prognostic value
  • Application of current therapeutics to the clinical scenario
  • Personalised therapies (may include but are not limited to)
    • BRAF inhibitors in melanoma
    • EGFR monoclonal antibodies (RAS) and hotspot mutations in KRAS and NRAS
    • Chemotherapy (MSI)
    • Detection of patients with Lynch syndrome (MSI/BRAF and MLH1 methylation) for colorectal cancers
  • NICE guidance and Standard Of Care testing
  • Clinical trials and their role in the diagnostic setting

Partnership of Genomics with other clinical specialisms

  • Multi-Disciplinary Team (MDT) working; Pathology, Histopathology, Genetics laboratory, Clinical Genetics and disease specific MDTs
  • Integrated reporting
  • Role of Clinical Genetics and onward referral
  • Impact of genomics on patients and their families including ethical considerations, including consent
  • Best Practise Guidelines, national guidance, clinical trials, advisory and regulatory bodies

 Horizon scanning

  • Translation of research findings into clinical practice
  • Future biomarkers and assessment of their clinical utility
  • New technologies (e.g. tumour mutation burden)