Genomics of acral lentiginous melanoma

Melanoma is the most aggressive type of skin cancer, causing about 75% of deaths from dermatological cancer. Acral lentiginous melanoma is the most common subtype of melanoma in mixed Latin American populations, but very few genomes and exomes from people of European descent have been analysed across several studies. This means that the genomic landscape of acral lentiginous melanoma is currently unknown and genomic analyses on strong predictors of survival such as ulceration are lacking. Additionally, no genes are known to increase the risk to this melanoma subtype.

We propose to target-sequence and analyse 550 tumour/normal acral lentiginous melanoma pairs and, as a comparison set, 500 sun-induced disease samples that have been collected over 35 years at the National Cancer Institute of Mexico. We will define the somatic landscape of acral lentiginous melanoma, looking particularly at the site of presentation (acral versus non-acral)  and whether it influences driver genes and mutation spectra, what somatic mutations co-occur in tumours and which are mutually exclusive. We will also look at how somatic mutations influence patient outcome and determine where genomic aberrations exist that are predictive of ulceration in acral lentiginous melanoma and whether there are germline genetic factors influencing susceptibility to acral lentiginous melanoma.