Scratching the surface: Gene signatures in pigmented skin lesions
Principal Investigator: Dr Neil Rajan
This project aims to support research that underpins the understanding of skin cancer in the elderly population by exploring how gene signatures in melanomas vary with age.
We want to develop a test that will allow a patient to know if a mole is benign or a type of skin cancer called melanoma, using a device that will simply scratch, sample and test the skin. We want this test to be available in primary care and we want a result in less than an hour.
This sounds like science fiction, but recent advances in the ability to biopsy the skin and detect small molecules such as DNA and RNA have made this a reality. In elderly patients, rapid diagnosis is important, as melanoma has a worse outcome in this group. However, the molecular “gene signature” melanoma is not fully understood, and that is what this study aims to discover. We plan to study melanomas from patients with increased genetic risk of melanoma to see if we can find “gene signatures” that will allow discrimination of cancer from benign pigmented lesions. This key bit of information is missing, but our preliminary research supports feasibility of discovering this from existing biopsies of tissue from such patients. We also plan to study melanomas in elderly patients to explore if the poorer prognosis seen in this group is due to different genetic factors in their melanomas.
If successful, our vision will reduce the time patients need to wait to find out if they have skin cancer, the number of operations needed, and their care pathway in the NHS.
There are several strategies to take data acquired at the end of this project forward to attract further funding:
- Molecular gene signatures found in this study will be captured as IP, and use of this to develop a grant application (eg i4i) to perform a clinical trial of microbiopsy analysis of pigmented skin lesions.
- Discovery of markers that will aid discrimination of melanomas and dysplastic naevi will be validated in an application for biomarker validation (eg biomarker project award- CRUK) in conjunction with the MRC pathological node.
- The sample set, gene expression data and clinical data set developed here, will be a valuable resource, and will inform and be utilised in future grant proposals of transcriptomic profiling of these samples using emerging techniques for archival FFPE whole tissue transcriptomics including RNAseq. The named CRA on this application will complete the majority of her laboratory work during the period funded by this grant. Her second year of funding will be supported by a one year Mohs surgical fellowship based in Newcastle, allowing her to carry out clinical research that relates to families with high risk of developing melanoma.
- Needle microdissection x 24 samples; RNA extraction x 24 samples; Nanostring assay x 24 samples; Preliminary data analysis.
- Needle microdissection x 120 samples; RNA extraction x 120 samples; Nanostring assay x 120 samples; Final data analysis.
- Validation of candidate genes QPCR; IHC validation.