A GWAS in uveal melanoma identifies risk polymorphisms in the CLPTM1L locus

Uveal melanoma, a rare malignant tumor of the eye, is predominantly observed in populations of European ancestry. A genome-wide association study of 259 uveal melanoma patients compared to 401 controls all of European ancestry revealed a candidate locus at chromosome 5p15.33 (region rs421284: OR = 1.7, CI 1.43–2.05). This locus was replicated in an independent set of 276 cases and 184 controls. In addition, risk variants from this region were positively associated with higher expression of CLPTM1L. In conclusion, the CLPTM1L region contains risk alleles for uveal melanoma susceptibility, suggesting that CLPTM1L could play a role in uveal melanoma oncogenesis.
Cancer: Risk allele identified for melanoma of the eye Researchers have discovered an important genetic risk variant linked to uveal melanoma, a rare malignant tumor of the eye. Marc-Henri Stern from Institut Curie in Paris, France, and colleagues compared more than 860,000 single DNA variants covering the entire genome, from the genomes of 259 people with uveal melanoma and 401 healthy controls, all of whom were of European ancestry. The researchers found that a series of closely linked gene variants on the short arm of chromosome 5 were significantly more common in the melanoma patients. They confirmed the association between this genomic region and disease risk in an independent cohort of 276 cancer cases and 184 controls. Expression analyses showed that the CLPTM1L gene contained in this region was more expressed in people with the risk variants, pointing to CLPTM1L playing a role in tumor development.