Document Type

Journal Article

Publication Title

eLife

ISSN

2050-084X

Volume

8

PubMed ID

30681412

Publisher

eLife Sciences Publications, Ltd

School

School of Medical and Health Sciences

RAS ID

28150

Funders

Melanoma Research Alliance Investigator Grant Award Number: 346859 2015-2018 Graeme J Walker

Comments

Originally published as: Ferguson, B., Handoko, H. Y., Mukhopadhyay, P., Chitsazan, A., Balmer, L., Morahan, G., & Walker, G. J. (2019). Different genetic mechanisms mediate spontaneous versus UVR-induced malignant melanoma. eLife, 8, Article e42424. Original publication available here

Abstract

Genetic variation conferring resistance and susceptibility to carcinogen-induced tumorigenesis is frequently studied in mice. We have now turned this idea to melanoma using the collaborative cross (CC), a resource of mouse strains designed to discover genes for complex diseases. We studied melanoma-prone transgenic progeny across seventy CC genetic backgrounds. We mapped a strong quantitative trait locus for rapid onset spontaneous melanoma onset to Prkdc, a gene involved in detection and repair of DNA damage. In contrast, rapid onset UVR-induced melanoma was linked to the ribosomal subunit gene Rrp15. Ribosome biogenesis was upregulated in skin shortly after UVR exposure. Mechanistically, variation in the ‘usual suspects’ by which UVR may exacerbate melanoma, defective DNA repair, melanocyte proliferation, or inflammatory cell infiltration, did not explain melanoma susceptibility or resistance across the CC. Instead, events occurring soon after exposure, such as dysregulation of ribosome function, which alters many aspects of cellular metabolism, may be important.

DOI

10.7554/eLife.42424

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Included in

Oncology Commons

Share

 
COinS