Abstract Number: 14

Driver mutations: phenotypic associations and prognostic significance

V. Mar

Meeting: 2014 Dermcoll

Session Information

Date: -

Session Title: Melanoma Symposium 1

Session Time: -

Recent molecular studies suggest two distinct groups of
cutaneous melanomas: those with a low mutation burden,
which tend to be BRAF or NRAS mutant; and those with a high (UV induced) mutation burden, which tend to be wildtype
for both BRAF and NRAS. Clinical and histological associations
of these two groups will be discussed. In a cohort of
196 patients with long-term follow-up, we were able to
show that patients with BRAF mutant tumors have poorer
survival than patients with BRAF/NRAS wild-type tumors
independent of other prognostic variables.
Interestingly, BRAF mutant tumors in this cohort were thinner at diagnosis and tended to grow more slowly compared to wild-type
tumors.
BRAF mutant tumors were also significantly thinner
in a larger cohort of 764 patients enrolled in the Melbourne
Melanoma Project, but were more likely to present with
nodal disease (P = 0.001). RAC1 mutations were also associated
with nodal disease at diagnosis (P = 0.03). The presence
of a dominant oncogene ‘drives’ tumor progression
and metastasis, but does not necessarily dictate the rate of
primary tumor growth or tempo of disease progression.