Genomic Landscape of Appendiceal Neoplasms.

Purpose: Appendiceal neoplasms are heterogeneous and are often treated with chemotherapy similarly to colorectal cancer (CRC). Genomic profiling was performed on 703 appendiceal cancer specimens to compare the mutation profiles of appendiceal subtypes to CRC and other cancers, with the ultimate aim to identify potential biomarkers and novel therapeutic targets.

Methods: Tumor specimens were submitted to a Clinical Laboratory Improvement Amendments-certified laboratory (Foundation Medicine, Cambridge, MA) for hybrid-capture-based sequencing of 3,769 exons from 315 cancer-related genes and 47 introns of 28 genes commonly rearranged in cancer. Interactions between genotype, histologic subtype, treatment, and overall survival (OS) were analyzed in a clinically annotated subset of 76 cases.

Results: There were five major histopathologic subtypes: mucinous adenocarcinomas (46%), adenocarcinomas (30%), goblet cell carcinoids (12%), pseudomyxoma peritonei (7.7%), and signet ring cell carcinomas (5.2%). (35% to 81%) and (8% to 72%) were the most frequent alterations in epithelial cancers; and mutations were significantly less frequent in appendiceal cancers relative to CRC. Low-grade and high-grade tumors were enriched for and mutations, respectively (both χ < .001). and were mutually exclusive (Bonferroni corrected < .001). Tumor grade and mutation status independently predicted OS. The mutation status of and strongly predicted OS (median, 37.1 months for mutant 75.8 - wild type 115.5 mutant; log-rank = .0031) and performed as well as grade in risk stratifying patients.

Conclusion: Epithelial appendiceal cancers and goblet cell carcinoids show differences in and mutation frequencies and have mutation profiles distinct from CRC. This study highlights the benefit of performing molecular profiling on rare tumors to identify prognostic and predictive biomarkers and new therapeutic targets.