This will be a prospective study recruiting patients who have been diagnosed wth advanced melanoma.

Participants will be asked to give informed consent before any samples are collected.

Participants will be asked to donate tissue and other biospecimens (see list below) that are surplus to clinical requirements if a participant is undergoing any of the following as part of their routine care:

• lymph node dissection
• sentinel lymph node biopsy as part of their normal care
• resection of metastatic skin lesions or visceral disease
• medical treatment for Stage IV disease Biospecimens include urine, stool, saliva, hair follicles, ascitic, pleural, pericardial or cerebrospinal fluid Collection of archival tumour tissue from previous biopsy/surgery that is surplus to clinical requirements will also be requested, where available.

Participants will be asked to consent to having easily accessible lesions biopsied or resected, which are not required for clinical reasons, but are for research purposes only. Participants can still be part of the study even if they do not agree to these extra, optional biopsies. Tissue samples from the surgical specimens and the original primaries will be examined to look for molecular markers to correlate with circulating tumour molecular markers.

Consent will be requested to grow cell lines from the donated tumour tissue and implant tumour tissue into mice to characterise the genetic changes seen in both CTCs and biopsies, in terms of resistance to targeted agents, in the lab setting. Consent to this part of the study will be optional.

A maximum of 50mls blood sample will be requested from participants before any intervention. Further blood samples (maximum of 50mls each time) will also be requested as follows:

• after surgery, on subsequent routine follow up at 3 months, and then 3 monthly thereafter (i.e. approximately 4 times in a year after the initial pre and post surgical specimens)
• at the time of disease recurrence
• If on treatment, then usually approximately 3 weeks after starting treatment, and then every 2 cycles of treatment
• at disease progression The samples will be tested for various circulating tumour biomarkers.

We will be asking a small group of patients, approx 20, to consent to weekly blood samples, for up to 8 weeks, for specific biomarker analyses.

Clinical data will be collected for each patient, looking at demographics, baseline haematology and biochemistry blood results, radiological extent of disease, time to disease progression, clinical and histological features of the primary. Patients will be followed up for approximately 10 years to assess their outcome.