Melanoma Focus Meeting 2012

Mutation Testing: Why, When, Which and How?

Melanoma Focus Meeting 2012

Why?

• Prognostic– BRAF?

• Predictive– Adjuvant • Ulceration?• Gene signature?

– Advanced disease• BRAF• RAS?• CKIT?

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

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

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

Melanoma Focus Meeting 2012

Multiplex testing

• Next generation sequencing• Chip based• Other kits

Aiming to5 working days turn around timeLess than £300

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

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