Molecular Pathology of Solid Neoplasms General Principles

Details

Title

Molecular Pathology of Solid Neoplasms General Principles

Type

Stage Two

Module code

HLS328

Requirement

Compulsory

Module objective

By the end of the training period trainees will, in respect to a thorough general understanding, theoretical and practical, of the knowledge, theoretical skills and clinical skills necessary to be proficient in the general principles of the molecular pathology of solid neoplasms, be able to:

• analyse, synthesise, evaluate and apply knowledge
• perform, adapt and master a range of technical and clinical skills and procedures and
• demonstrate the attitudes and behaviours necessary for professional practise as a Consultant Clinical Scientist dealing with the complexities, uncertainties and tensions of professional practise at this level.

Knowledge and understanding

By the end of the training period the trainee will be able to demonstrate the ability to analyse, evaluate and synthesise relevant knowledge and its application to their professional practice in relation to:

• Understanding of DNA structure and gene expression, organisation of the human genome, inheritance, mutation mechanisms
• Core knowledge and understanding of human molecular genetics and the molecular basis of many diseases
• Understanding of the genetic abnormalities associated with solid tumour biology and, in particular:
  • Carcinogenesis – the importance of viruses and chemicals and how these relate to the prevention, diagnosis and treatment of
  • The molecular defects than are common to all cancers and the mechanisms underlying these
    1. Self-sufficiency in growth signals
    2. Insensitivity to anti-growth signals
    3. Evading apoptosis
    4. Limitless replicative potential
    5. Tissue invasion and metastasis
    6. Sustained angiogenesis
    7. Dysregulation of metabolism
    8. Avoiding immune destruction
    9. Tumour promotion by inflammation
    10. Genomic instability and mutation
  • Understanding of the pathways required for cancers to survive and grow, particularly:
    1. Growth factors and their receptors, including EGFR, HER2, and C-Kit
    2. Downstream intracellular signalling pathways, including molecules such as BRAF, KRAS, AKT and MTOR
    3. Tumour suppressor genes – p53, RB, p16, p21
    4. Others
  • Methodology, principles and practice, assay design, trouble-shooting: PCR, linkage analysis, mutation screening, DNA sequencing, single-biomarker and multiple-biomarker testing

Technical and clinical skills

By the end of the training period the trainee will be able to demonstrate a critical understanding of current relevant research, theory and knowledge and its application to the performance, adaptation and mastery of the following skills:

• Knowledge of technical and practical aspects of molecular biology methods for the investigation of solid tumour malignancies
• Demonstrates appropriate use of molecular biology investigations to establish diagnosis and to produce a fully interpretative clinical diagnostic laboratory report

These technical skills require two epistemological frameworks that are exclusive to molecular diagnostics of solid tumours, namely:

• To acquire a set of histomorphology skills for the understanding and delivery of molecular testing
• To understand the diagnostic opportunities and technological limitations of working with formalin-fixed, paraffin embedded (FFPE) material
• To be confident in both tissue-based hybridization techniques and PCR-based techniques, and understand when a specific approach carries the outmost diagnostic significance.

By the end of the training period the trainee will be able to apply knowledge of the general principles of the molecular pathology of solid neoplasms to perform, adapt and master the clinical skills necessary to manage and to understand the:

• The interpretative report – develop knowledge of the clinical parameters governing the interpretation of a result and how these need to be discussed in the diagnostic report
• Diagnostic relevance of new tests – develop an understanding to evaluate when a certain test carries sufficient diagnostic, prognostic and/or therapeutic information to be considered for validation
• Clinical value of molecular tests – understand when molecular tests have diagnostic, prognostic or therapeutic value, and how this affects the validation and interpretation
• Clinical discussion – develop the understanding of the different components of a clinical/therapeutic decision making in an MDT and how/when is the discussion of the molecular test of relevance