Anatomic position determines oncogenic specificity in melanoma.

ABSTRACT: Oncogenic alterations to DNA are not transforming in all cellular contexts^1,2. This may be due to pre-existing transcriptional programmes in the cell of origin. Here we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet or under the nails³. We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma and enrichment for CRKL amplifications in acral melanoma. We modelled these changes in transgenic zebrafish models and found that CRKL-driven tumours formed predominantly in the fins of the fish. The fins a

SUBMITTER: Weiss JM 

PROVIDER: S-EPMC9355078 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature