Cancer —
Training activity: 5

Details

Select, analyse, interpret and report the appropriate genomic tests for patients referred with germline cancer susceptibility for Lynch syndrome.

Type

Developmental training activity (DTA)

Evidence requirements

Evidence the activity has been undertaken by the trainee​.

Reflection on the activity at one or more time points after the event including learning from the activity and/or areas of the trainees practice for development.

An action plan to implement learning and/or to address skills or knowledge gaps identified.

Reflective practice guidance

The guidance below is provided to support reflection at different time points, providing you with questions to aid you to reflect for this training activity. They are provided for guidance and should not be considered as a mandatory checklist. Trainees should not be expected to provide answers to each of the guidance questions listed.

Before action

What are the intended outcomes of the training activity?

• Do you have a clear understanding of the laboratory testing strategy required for Lynch syndrome (e.g., germline sequencing of mismatch repair genes MLH1, MSH2, MSH6, and PMS2, plus EPCAM deletion analysis) and how to accurately analyse, interpret, and report these findings for germline cases?
• How will you apply your integrative knowledge of laboratory techniques (such as correlating somatic IHC/MSI results with germline sequencing or MLPA) to investigate these cases?
• What steps will you take to ensure you can demonstrate appropriate communication skills to present these germline findings clearly to clinical colleagues, such as oncologists or genetic counsellors?
• What foundational knowledge regarding germline variant classification (e.g., ACGS/ACMG guidelines) and clinical referral criteria do you need to acquire before embarking on this activity?

What do you anticipate you will learn from the experience?

• What specific insights do you hope to gain regarding the clinical significance of germline findings (e.g., distinguishing between pathogenic variants and variants of uncertain significance) and their impact on both the patient and their family members (cascade testing)?
• Thinking about what you already know, which aspects of Lynch syndrome diagnostics—such as managing complex structural variants—do you find most challenging or interesting to explore?

What actions will you take in preparation for the experience?

• How will you gain clarity on the germline testing pathway and the expectations for your case presentation?
• What challenges do you anticipate (e.g., interpreting complex intronic variants, addressing constitutional MLH1 methylation, or explaining the limitations of current assays), and how have you planned to handle them?
• How do you feel about embarking on this activity, considering the significant life-long implications that a germline diagnosis has for the patient and their relatives?

In action

What are you doing?

• How are you currently approaching the selection and analysis of germline tests for Lynch syndrome (e.g., sequencing MLH1, MSH2, MSH6, PMS2, and EPCAM deletion analysis), and what real-time decisions are you making to ensure the strategy matches the clinical referral?
• Which aspects of the germline analysis feel intuitive, and where are you consciously relying on specific variant classification guidelines (such as ACGS/ACMG) right now?

How are you progressing with the activity?

• How effective are your actions in achieving the germline profiling of the case, and what technical challenges—such as interpreting complex intronic variants or structural alterations—are you encountering?
• How are you applying integrative knowledge of different laboratory techniques (e.g., correlating somatic IHC/MSI data with germline sequencing and MLPA) as the data unfolds to ensure a comprehensive investigation?

How are you adapting to the situation?

• What immediate support or alternative methodologies do you need to resolve ambiguous results, such as constitutional MLH1 methylation or variants of uncertain significance (VUS), as they arise?
• How are you ensuring your communication of these findings to clinical colleagues is clear, accurate, and remains within your professional scope of practice?

On action

What did you notice?

• Summarise the key points of the Lynch syndrome referral and the specific laboratory testing strategy (e.g., germline sequencing of MLH1, MSH2, MSH6, PMS2, and EPCAM deletion analysis) you selected to investigate the case.
• What were the primary genetic findings (such as pathogenic variants or variants of uncertain significance), and were there any clinical details or prior somatic results (e.g., IHC or MSI status) that significantly influenced your final analysis?

What did you learn from the activity?

• How did you improve your ability to integrate knowledge across different techniques, such as correlating somatic pathology findings with germline molecular data, to provide a comprehensive interpretation?
• What insights did you gain from managing technical challenges—such as interpreting complex intronic variants or addressing constitutional methylation—and how did your reflection-in-action influence the final reporting of the case?

What will you take from the experience moving forward?

• How will you apply the learning from this activity to your routine practice to ensure germline cancer susceptibility results are communicated clearly and accurately to clinical colleagues and genetic counsellors?
• What specific next steps or resources (e.g., updated variant classification guidelines or senior consultation) have you identified to further develop your skills in presenting complex germline investigations within a multidisciplinary context?

Beyond action

Have you revisited the experiences?

• How has your perspective on selecting Lynch syndrome testing strategies (e.g., germline sequencing vs. MLPA) evolved as you have gained more experience with other germline cancer referrals?
• Have discussions with peers or colleagues changed how you view your earlier interpretations of complex Lynch syndrome findings, such as variants of uncertain significance (VUS) or constitutional MLH1 methylation?
• Compare this experience with your Observed Training Activities—what specific laboratory behaviours and analytical practices for germline susceptibility profiling have you now assimilated into your routine workflow?

How have these experiences impacted upon your current practice?

• How has your integrative knowledge of Lynch syndrome (e.g., correlating somatic IHC/MSI with germline results) informed your current problem-solving when investigating other hereditary cancer syndromes?
• In what ways are you now applying the communication and presentation skills developed during this activity to your wider interactions with clinical genetics colleagues and the multidisciplinary team (MDT)?
• How is the learning from these Lynch syndrome cases helping you prepare for upcoming Case-based Discussions (CBDs) or other in-person assessments for this module?

How might these experiences contribute towards your future practice?

• What transferable skills—such as applying ACGS/ACMG variant classification guidelines or translating complex germline data into clear clinical reports—will be most valuable as you progress toward becoming a Clinical Scientist?
• How will the principles learned here help you adapt to future advancements in Lynch syndrome diagnostics, such as the increasing use of whole-genome sequencing or refined functional assays?
• What clear actions have you identified to continue developing your expertise in clinical genetics and the molecular investigation of germline cancer susceptibility?

Relevant learning outcomes

#	Outcome
# 2	Outcome Select the laboratory testing strategy, analyse, interpret and report tests for patients referred with germline cancer.
# 4	Outcome Apply integrative knowledge of laboratory techniques applied to the investigation of cases referred for cancer.
# 5	Outcome Demonstrate appropriate communication skills to present the results of investigations into acquired and germline cancer cases clearly to healthcare professional colleagues.