{Reference Type}: Journal Article
{Title}: Expanding the landscape of oncogenic drivers and treatment options in acral and mucosal melanomas by targeted genomic profiling.
{Author}: Turner JA;Van Gulick RJ;Robinson WA;Mughal T;Tobin RP;MacBeth ML;Holman B;Classon A;Bagby SM;Yacob BW;Hartman SJ;Silverman I;Vorwald VM;Gorden N;Gonzalez R;Gay LM;Ali SM;Benson A;Miller VA;Ross JS;Pitts TM;Rioth MJ;Lewis KD;Medina T;McCarter MD;Gonzalez R;Couts KL;
{Journal}: Int J Cancer
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jul 12
{Factor}: 7.316
{DOI}: 10.1002/ijc.35087
{Abstract}: 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.