Comprehensive Genomic Profiling of Advanced Esophageal Squamous Cell Carcinomas and Esophageal Adenocarcinomas Reveals Similarities and Differences

Abstract

Background. Esophageal squamous cell carcinomas (ESCCs) and esophageal adenocarcinomas (EACs) account for .95% of esophageal malignancies and represent a major global health burden. ESCC is the dominant histology globally but represents a minority of U.S. cases, with EAC accounting for the majority of U.S. cases.The patient outcomes for advanced ESCC and EAC are poor, and new therapeutic options are needed. Using a sensitive sequencing assay, we compared the genomic profiles of ESCC and EAC with attention to identification of therapeutically relevant genomic alterations. Methods. Next-generation sequencing-based comprehensive genomic profiling was performed on hybridization-captured, adaptor ligation-based libraries to a median coverage depth of .6503 for all coding exons of 315 cancer-related genes plus selected introns from 28 genes frequently rearranged in cancer.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.Results. There were no significant differences by sex for either tumor type, and the median age for all patients was 63 years.

Molecular predictive markers in tumors of the gastrointestinal tract

“…However the reported frequency of somatic mutations identified appears to be low and this is obvious when accessing data from the Catalogue of Somatic Mutations in Cancer database (COSMIC, cancer.sanger.ac.uk) (Figure 1), which is currently the most comprehensive global resource accessing the world literature on somatic mutations in human cancer[12]. In a recent study, NGS-based comprehensive genomic profiling was used to analyze ESCC and EAC tumors[13]. The analysis showed that the esophageal histotypes differ significantly in genomic alterations profile, with KRAS and ERBB2 far more frequently altered in EAC compared to ESCC.…”

“…Bar chart showing the copy number variations in esophageal cancer according to the study performed[13]. In the Y-axis the percentage of CNV frequency is represented.…”

“…EGFR is frequently overexpressed in ESCCs, while HER2 overexpression occurs mainly in EACs. Thus the trastuzumab-platinum regimen is currently used for the 15% of the EACs patients that test positive for HER2 (ERBB2) amplification or overexpression[13,14]. …”

New Strategies in Esophageal Carcinoma: Translational Insights from Signaling Pathways and Immune Checkpoints

“…Another, more recently published genomic profiling study of SCC and esophageal adenocarcinoma by Wang and colleagues (29), in which next-generation sequencing was performed on coding exons from 315 cancer-related genes plus selected introns of 28 genes frequently rearranged in cancer, suggested similar rates of "clinically relevant" genomic alterations between the two, but with differing profiles. SCC more frequently harbored PIK3CA and PTEN mutations, in addition to NOTCH1, whereas esophageal adenocarcinoma showed higher rates of KRAS mutations and HER2 amplification.…”

Targeted Treatment of Esophagogastric Cancer

“…Indeed, outcomes in chemotherapy trials were similar in patients with squamous cell carcinomas and adenocarcinomas [4,5,6]. This has been changing theoretically with the discovery of molecular differences between histologies and practically with the advent of targeted agents solely approved for esophagogastric adenocarcinomas [7]. …”