%0 Journal Article
%T Expanding the landscape of oncogenic drivers and treatment options in acral and mucosal melanomas by targeted genomic profiling.
%A Turner JA
%A Van Gulick RJ
%A Robinson WA
%A Mughal T
%A Tobin RP
%A MacBeth ML
%A Holman B
%A Classon A
%A Bagby SM
%A Yacob BW
%A Hartman SJ
%A Silverman I
%A Vorwald VM
%A Gorden N
%A Gonzalez R
%A Gay LM
%A Ali SM
%A Benson A
%A Miller VA
%A Ross JS
%A Pitts TM
%A Rioth MJ
%A Lewis KD
%A Medina T
%A McCarter MD
%A Gonzalez R
%A Couts KL
%J Int J Cancer
%V 0
%N 0
%D 2024 Jul 12
%M 39001563
%F 7.316
%R 10.1002/ijc.35087
%X Despite advancements in treating cutaneous melanoma, patients with acral and mucosal (A/M) melanomas still have limited therapeutic options and poor prognoses. We analyzed 156 melanomas (101 cutaneous, 28 acral, and 27 mucosal) using the Foundation One cancer-gene specific clinical testing platform and identified new, potentially targetable genomic alterations (GAs) in specific anatomic sites of A/M melanomas. Using novel pre-clinical models of A/M melanoma, we demonstrate that several GAs and corresponding oncogenic pathways associated with cutaneous melanomas are similarly targetable in A/M melanomas. Other alterations, including MYC and CRKL amplifications, were unique to A/M melanomas and susceptible to indirect targeting using the BRD4 inhibitor JQ1 or Src/ABL inhibitor dasatinib, respectively. We further identified new, actionable A/M-specific alterations, including an inactivating NF2 fusion in a mucosal melanoma responsive to dasatinib in vivo. Our study highlights new molecular differences between cutaneous and A/M melanomas, and across different anatomic sites within A/M, which may change clinical testing and treatment paradigms for these rare melanomas.