Servizio Comunitario di Informazione in materia di Ricerca e Sviluppo - CORDIS

Demonstration that experimentally induced nevi in Ink4a/Arf knockout mice does rarely progress to melanoma

The main results ('deliverables) of our activity on induction of melanocytic hyperplasia (moles/nevi) and tumours (melanomas) are:

- 1 - "Experimentally induced nevi in Ink4a/Arf knock out mice do not, or only rarely, progress to melanoma". (Implying that essential oncogenic alterations, gene mutations, may still be lacking in these UV-induced nevi).

- 2 - " The dark pigment (eumelanin) in the mice is likely to protect very strongly against melanoma initiation/progresssion".

Notes:

Sub - 1 - dysfunctional INk4a/Arf is related to familial melanoma, and expression of the p16/Ink4a protein is commonly low in melanoma, but surprisingly, the nevi that arise with a dysfunction in these proteins do not show a high rate of progression toward malignant melanoma. In micro-dissections of the nevi will check for mutations in the oncogenes Braf and N- (K-. H-) ras, commonly found mutated in human nevi and melanocytes.
Sub - 2 - A possibly low level of UV-induced genotoxic damage to the melanocytes containing eumelanin in our mice explains why we did not see a high rate of induction of melanoma, in contrast to recent experiments ran by others who worked with transgenic albino mice who did develop amelanotic melanoma.

Reported by

Leiden University Medical Centre
Postal Zone S2P
2300 RC Leiden
Netherlands