Decoding complex patterns of genomic rearrangement in hepatocellular carcinoma ☆

摘要

Elucidatingthemolecularbasisofhepatocellularcarcinoma(HCC)iscrucialtodevelopingtargeteddiagnosticsandtherapiesforthisdeadlydisease.Thelandscapeofsomaticgenomicrearrangements(GRs),whichcanleadtooncogenicgenefusions,remainspoorlycharacterizedinHCC.Wehavepredicted4314GRsincludinglarge-scaleinsertions,deletions,inversionsandtranslocationsbasedonthewhole-genomesequencingdatafor88primaryHCCtumoron-tumortissues.Weidentifiedchromothripsisin5HCCgenomes(5.7%)recurrentlyaffectingchromosomalarms1qand8q.Albumin(emALB/em)wasfoundtoharborGRs,deactivatingmutationsanddeletionsin10%ofcohort.Integrativeanalysisidentifiedapatternofpairedintra-chromosomaltranslocationsflankingfocalamplificationsandasymmetricalpatternsofcopynumbervariationflankingbreakpointsoftranslocations.Furthermore,wepredicted260genefusionswhichfrequentlyresultinaberrantover-expressionofthe3prime;genesintumorsandvalidated18genefusions,includingrecurrentfusion(2/88)ofemABCB11/emandemLRP2/em./p/div