BACKGROUND: @entity4310 with specific genetic drivers account for a subset of @entity1636 ( @entity1636 ), but the genomic underpinnings of sporadic cases remain poorly understood. Recent advances in copy number variation ( @entity471 ) prediction from exome sequencing are facilitating exploration of genomic rearrangements common to these @entity189 . METHODS: ACC and matched, nontumor samples underwent exome sequencing. CNVs were predicted using coverage-depth comparison. Clinicopathologic characteristics of amplification- and deletion-dominant samples were compared and pathway enrichment analysis performed for regions with significant variation. RESULTS: CNVs are distributed broadly across the ACC genome. Individual signatures demonstrate amplification or deletion dominance. Areas of recurrent amplification include chromosomes 5, 12, 19, and 20, whereas chromosomes 1, 10, 18, and 22 are deletion prone. Large-scale amplification of chromosome 19 occurred in 12 of 19 cases (63%), including 6 of 8 amplification-dominant samples (75%) and was associated with stage III/IV disease (P  =  .002). Genes within this amplified region are overrepresented among the @entity774 and @entity479 biosynthesis pathways (P  =  4.2(-5) and 2.5(-5), respectively). CONCLUSION: @entity471 detection via exome sequencing allows high-resolution cataloging of structural variations in ACC. Large-scale, recurrent amplifications encompassing known adrenal-specific gene pathways correlate with @entity5 stage. Further functional analysis of individual genes within these regions could provide mechanistic insight into specific drivers underlying pathogenesis and progression of ACC.

Chromosome 19 amplification correlates with advanced disease in XXXX .

@entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity189 :: ('MESH:D002277', 'Disease') :: ['carcinomas'] @entity471 :: ('12143', 'Species') :: ['CNV'] @entity1636 :: ('MESH:D018268', 'Disease') :: ['adrenocortical carcinomas', 'ACCs'] @entity479 :: ('D013256', 'Chemical') :: ['steroid'] @entity4310 :: ('MESH:D009386', 'Disease') :: ['Familial syndromes'] @entity774 :: ('MESH:D000312', 'Disease') :: ['adrenal hyperplasia']
@entity1636 :: (MESH:D018268,Disease) :: ['adrenocortical carcinoma']
