Genomic Profiling of XXXX Reveals New Opportunities for Targeted Therapy.

@entity1 @entity986 @entity5 @entity470 @entity957 @entity4910 @entity8985 @entity3 @entity8498
UNASSIGNED: @entity957 ( @entity957 ) is a rare @entity5 for which there are limited treatment options due to a poor understanding of the molecular alterations underlying disease development and progression. Therefore, we performed comprehensive, targeted next-generation sequencing to identify relevant somatic genomic alterations in a retrospective cohort of 60 fixed @entity5 samples from 43 @entity957 cases (including 14 matched primary/ @entity3 pairs). We identified a median of two relevant somatic mutations and one high-level copy-number alteration per sample (range, 0-5 and 0-6, respectively). Expression of HPV and @entity986 was detectable in 12% and 28% of @entity1 , respectively. Furthermore, advanced clinical stage, lack of @entity986 expression, and MYC and @entity4910 amplifications were significantly associated with shorter time to progression or @entity957 -specific survival. Notably, four cases harbored @entity470 amplifications and one demonstrated @entity8985 amplification, genes for which approved and investigational targeted therapies are available. Importantly, although paired @entity5 and lymph node @entity3 were largely homogeneous for relevant somatic mutations, we identified heterogeneous @entity470 amplification in primary @entity5 /lymph node @entity3 in 4 of 14 cases, despite uniform @entity470 protein overexpression. Likewise, activating @entity8498 mutations occurred in 8 of 43 cases. Taken together, we provide the first comprehensive molecular @entity957 analysis, which offers new insight into potential precision medicine approaches for this disease, including strategies targeting @entity470 . @entity5 Res; 75(24); 5219-27.   2015 AACR.
