1. Melanoma Focus Meeting 2012 Mutation Testing: Why, When, Which and How?

2. Melanoma Focus Meeting 2012 Why? Prognostic – BRAF? Predictive – Adjuvant Ulceration? Gene signature? – Advanced disease BRAF RAS? CKIT?

3. Melanoma Focus Meeting 2012 When Advanced disease – Drive therapeutic decision – Clonal evolution – Delays and/or failed biopsy Primary resection – Never needed – ‘Waste’ sample, better technology – Generate anxiety

4. Melanoma Focus Meeting 2012 Molecular testing in diagnostic samples Type of specimen: any – Formalin fixed-paraffin embedded: Biopsy Surgical – Cytology: ++ Needle washings (avoiding smears) Type of test: – DNA based: mutation testing: BRAF, NRAS, KIT, etc,.. – RNA based: translocation, level of expression – Gene amplification: in situ hybridization: FISH, SIH, CISH

5. Melanoma Focus Meeting 2012 Which alterations? Currently, routine practice: BRAF and/or KIT mutation testing CR UK stratified medicine: BRAF, KIT, NRAS, PIK3CA Near future: whatever is clinically relevant

6. Melanoma Focus Meeting 2012 Multiplex testing Next generation sequencing Chip based Other kits Aiming to 5 working days turn around time Less than £300

7. Melanoma Focus Meeting 2012 Pathway Molecular testing – As soon as possible (molecular tests can be diagnostic, prognostic and predictive) – Ideally, at the time of diagnosis, part of histology assessment Can be performed retrospectively: material is banked – Paraffin blocks stored for 30 years – Extracted DNA and RNA also banked

8. Melanoma Focus Meeting 2012 Melanoma Quality Standards 2012 People with ≥Stage IIIB melanoma, should be offered genotyping of their melanoma to allow planning of systemic treatment by the multidisciplinary team