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A mutation in the Cdon gene potentiates congenital nevus development mediated by NRAS Q61K
Author(s) -
Chitsazan Arash,
Ferguson Blake,
Ram Ramesh,
Mukhopadhyay Pamela,
Handoko Herlina Y.,
Gabrielli Brian,
Soyer Peter H,
Morahan Grant,
Walker Graeme J.
Publication year - 2016
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12487
Subject(s) - neuroblastoma ras viral oncogene homolog , biology , sonic hedgehog , genetics , nevus , cancer research , gene , mutation , melanoma , kras
Summary Congenital nevi develop before birth and sometimes cover large areas of the body. They are presumed to arise from the acquisition of a gene mutation in an embryonic melanocyte that becomes trapped in the dermis during development. Mice bearing the Cdk4 R24C ::Tyr‐ NRAS Q61K transgenes develop congenital nevus‐like lesions by post‐natal day 10, from melanocytes escaping the confines of hair follicles. We interbred these mice with the collaborative cross ( CC ), a resource that enables identification of modifier genes for complex diseases (those where multiple genes are involved). We examined variation in nevus cell density in 66 CC strains and mapped a large‐effect quantitative trait locus ( QTL ) controlling nevus cell density to murine chromosome 9. The best candidate for a gene that exacerbates congenital nevus development in the context of an NRAS mutation is Cdon , a positive regulator of sonic hedgehog (Shh) that is expressed mainly in keratinocytes.