ComprehensiveGenomicProfilingofAdvancedEsophagealSquamous CellCarcinomasandEsophagealAdenocarcinomasRevealsSimilarities and Differences

Background. Esophageal squamous cell carcinomas (ESCCs) andesophagealadenocarcinomas(EACs)accountfor.95%of esophageal malignancies and represent a major global health burden.ESCCisthedominanthistologygloballybutrepresents aminorityofU.S.cases,withEACaccountingforthemajorityof U.S.cases.ThepatientoutcomesforadvancedESCCandEACare poor,andnewtherapeuticoptionsareneeded.Usingasensitive sequencing assay, we compared the genomic profiles of ESCC and EAC with attention to identification of therapeutically relevantgenomic alterations. Methods. Next-generation sequencing-based comprehensive genomic profiling was performed on hybridization-captured, adaptor ligation-based libraries to a median coverage depth of.6503forallcodingexonsof315cancer-relatedgenesplus selectedintronsfrom28genesfrequentlyrearrangedincancer. Results from a single sample were evaluated for all classes of genomic alterations (GAs) including point mutations, short insertions and deletions, gene amplifications, homozygous deletions, and fusions/rearrangements. Clinically relevant genomic alterations (CRGAs) were defined as alterations linked to approved drugs and those under evaluation in mechanismdriven clinical trials.