Genomics of Sporadic Cancers

Module details

Title

Genomics of Sporadic Cancers

Type

Specialist

Module code

SLS423

Credits

15

Requirement

Compulsory

Aim of this module

This module will provide the trainee with knowledge and understanding of the role and application of genetic and genomic testing in the diagnosis and management of patients with sporadic cancers.

 

The content for this module will focus on (as exemplars) patients who present with acquired cancers including Chronic Myeloid Leukaemia (CML), Acute Lymphoblastic Leukaemia (ALL), Acute Myeloid Leukaemia (AML), sporadic colorectal cancer and lung cancer.

Competencies

#	Learning outcome	Competency	Action
# 1	Learning outcome 1,2	Competency Select the correct genetics test for patients referred with acquired cancer. As examples: sporadic colorectal cancer, lung cancer and leukaemia (CML, ALL and AML).	Action View
# 2	Learning outcome 1,2,3	Competency Perform gene fusion analysis using appropriate current technology on oncology samples. As examples: sporadic colorectal cancer, lung cancer and leukaemia (CML, ALL and AML).	Action View
# 3	Learning outcome 1,2,4	Competency Perform whole genome analysis on samples from patients with leukaemia at diagnosis. Examples CML, ALL and AML.	Action View
# 4	Learning outcome 1,2,3	Competency Perform appropriate molecular testing on various cancer samples.	Action View
# 5	Learning outcome 1,2,3	Competency Perform appropriate genetic testing for monitoring and measurement of disease in relation to both treatment and prognosis.	Action View
# 6	Learning outcome 5,6	Competency Interpret and report on a range of genetic testing in haematological malignancy, including both diagnostic and follow-up (monitoring) analysis.	Action View

Assessments

You must complete:

• 2 case-based discussion(s)
• 2 of the following DOPS/ OCEs:

Perform duty scientist checking of samples referred for acquired cancer	DOPS
Analyse chromosomes from a routine haematological malignancy	DOPS
Interpret the results of analysis to monitor Minimal Residual Disease	DOPS
Analyse the results of RQ PCR analysis	DOPS
Analyse the results of gene fusion testing by FISH	DOPS
Analyse the results of microsatellite analysis for monitoring bone marrrow transplantation	DOPS
Analyse results generated by Next Generation Sequencing	DOPS
Use bioinformatic tools to interpret the clinical significance of a sequence variant	DOPS
Prepare a clinical report for a patient referred with an aquired cancer	DOPS
Assess microsatellite results from a colorectal cancer sample for a mismatch repair defect	DOPS
Participate in an MDT meeting with other healthcare professionals	OCE
Take a patient history can be undertaken in virtual patient environment	OCE
Discuss patient results with a healthcare professional telephone or in person	OCE

Learning outcomes

1. Apply appropriate sample selection criteria, taking into account the implications of acquired sporadic cancer with respect to sampling mixed cell populations, limits of detection, sensitivity of assay and patient management.
2. Apply an appropriate testing strategy for the commonly referred acquired sporadic cancers at all stages of the patient pathway.
3. Perform targeted testing for patients referred with sporadic cancer.
4. Perform whole genome testing for patients referred with sporadic cancer.
5. Analyse the results from genetic and genomic testing in  acquired sporadic cancers.
6. Interpret and report a range of genetic and genomic testing relevant to acquired sporadic cancer.

Learning outcomes

1. Explain the difference between the utilisation of genetic and genomic testing in acquired disease compared with inherited disease with specific reference to diagnosis, prognosis, monitoring and treatment.
2. Explain the challenges of the analysis of mixed cell populations and sampling for testing.
3. Explain the clinical presentation and assessment of patients with the common referrals for acquired cancers: Chronic Myeloid Leukaemia (CML), Acute Lymphoblastic Leukaemia (ALL), Acute  Myeloid Leukaemia (AML), sporadic colorectal cancer and lung cancer.
4. Discuss and evaluate appropriate genetic and genomic testing strategies for the above acquired cancers throughout the life of the patient and with reference to other testing modalities.
5. Describe the design, operation and performance of a range of genetic and genomic testing relevant to cancer.
6. Discuss the implications of the genomic tests considering diagnosis, prognosis and treatment of cancer patients within a patient-centred service, considering the views and wishes of patients and their families.
7. Discuss the partnership between genetics services and other clinical specialisms (Histopathology, Haematology and Oncology) in the cancer patient’s care pathways and the impact of national and international guidance.
8. Describe the role of clinical trials and the requirements for genetic and genomic testing therein.

Indicative content

Scientific basis of cancer development

• The role of Loss of Heterozygosity (LoH)
• Knudson's two hit hypothesis
• Methylation in cancer development

 Clinical presentation and assessment of patients

• Clinical presentation of patients with common referrals for acquired cancers: CML, ALL, AML, sporadic colorectal cancer and lung cancer
• Diagnosis of cancer using a multidisciplinary approach
• Clinical presentation and assessment of patients with known acquired cancers
• Genetic causes of sporadic cancer such as sporadic colorectal cancer, the gene pathways involved and their relation to inherited disease
• Difference between the utilisation of genetic and genomic testing in acquired disease compared with inherited disease

 Genetic laboratory testing strategies

• Laboratory testing pathway including reflex testing
• Design, operation and performance of a range of genetic tests
• The use and limitations of a range of sample types to analyse tumour DNA including:
  • formalin fixed paraffin embedded material
  • fresh frozen tumour tissue
  • cell free circulating tumour DNA
  • bone marrow and peripheral blood
• Challenges of the analysis of mixed cell populations and sampling for testing
• The principles of cost effectiveness in regards to the tests used
• Testing methodology including limitations and sensitivity
• “hot-spot” mutations, including Sanger sequencing, pyrosequencing and real time PCR
• Next generation sequencing (NGS) panels for multiple cancer genes (advantages and challenges)
• Principles of FISH and chromosome analysis in identification of genetic changes associated with cancer
• Rearrangements and translocations commonly associated with solid tissue cancer and the named leukaemic types, their clinical significance and the methods used to detect them
• Bioinformatics for the processing of large datasets
• Interpret archived results based on older technologies and discuss the implication and limitation of these results for the patient and family
• Awareness of the importance of turnaround time in the pathway of care
• Role of multidisciplinary team (MDT) meetings and international guidance such as Improving Outcomes Guidance and NICE guidelines in the cancer patient care pathways

 Clinical scientific, ethical and legal considerations

• Consent for testing and sample storage
• National guidelines
• Follow-up management including repeat testing for disease monitoring

 Interpretation and reporting of results to include:

• Diagnosis of cancer
• Cancer prognosis and clinical care pathways associated with precision medicine
• Treatment monitoring
• Utility of genetic and genomic testing in monitoring the efficacy of treatment in cancer and named leukaemic types (including bone marrow transplantations)
• Disease monitoring and the principles underpinning quantitation of residual disease, e.g. CML, ALL
• Use of current actionable genetic biomarkers in the management and treatment of cancer
• The basis of large scale national and international projects focused on cancer and the importance of clinical trials

Activities

• Observe bone marrow sampling. Critically reflect on your observation and discuss the implications for sample management with your supervisor.
• Observe pathological dissection in histopathology and identify the implications for tissue sampling and mixed cell populations.
• Attend and participate in a relevant MDT and identify the role and importance of these in the management of patients and the patient pathway.

 

• Gain experience of the following and reflect on their importance, application and effect on patient management:
• FISH analysis using the appropriate probes.
• Chromosomal analysis on samples from patients with CML, ALL and AML.
• Appropriate molecular testing on various cancer samples to include both genotyping assays for single or small numbers of mutations and NGS panels for “hot-spot” mutations.