Exome Sequencing of ABCB5 Identifies Recurrent Melanoma Mutations that Result in Increased Proliferative and Invasive Capacities.

ABSTRACT: ABCB5 is an ABC transporter that was shown to confer low-level multidrug resistance in cancer. In this study, we show that ABCB5 was mutated in 13.75% of the 640 melanoma samples analyzed. Besides nonsense mutations, two mutation hotspots were found in the ABCB5 protein, in the drug-binding pocket and the nucleotide-binding domains. Four mutations, which are representative of the mutation pattern, were selected. ATPase assays showed that these mutations resulted in a decrease in basal ATP hydrolysis by ABCB5. To select informative melanoma cell lines, mutational profiles of the clinical samples were further analyzed. This study showed mutations in the tumor suppressor CDKN2A gene and the NRAS oncogene in 62.5% and 75%, respectively of the samples that had mutations in the ABCB5 gene. No mu

SUBMITTER: Sana G 

PROVIDER: S-EPMC6708748 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature