Tracking the Genomic Evolution of Esophageal Adenocarcinoma through Neoadjuvant Chemotherapy

• DOI: 10.1158/2159-8290.cd-15-0412
• Publication Date: 2015-05-25T05:53:38Z
• Authors: Nirupa Murugaesu; Gareth A. Wilson; Nicolai J. Birkbak; Thomas B.K. Watkins; Nicholas McGranahan; Sacheen Kumar; Nima Abbassi-Ghadi; Max Salm; Richard Mitter; Stuart Horswell; Andrew Rowan; Benjamin Phillimore; Jennifer Biggs; Sharmin Begum; Nik Matthews; Daniel Hochhauser; George B. Hanna; Charles Swanton
• Keywords: Exome

Esophageal adenocarcinomas are associated with a dismal prognosis. Deciphering the evolutionary history of this disease may shed light on therapeutically tractable targets and reveal dynamic mutational processes during course following neoadjuvant chemotherapy (NAC). We exome sequenced 40 tumor regions from 8 patients operable esophageal adenocarcinomas, before after platinum-containing NAC. This revealed genomic landscape presence heterogeneous driver mutations, parallel evolution, early genome-doubling events, an association between high intratumor heterogeneity poor response to Multiregion sequencing demonstrated significant reduction in thymine guanine mutations within CpTpT context when comparing late platinum signature enrichment cytosine adenine CpC characterized by chromosomal instability leading amplifications containing targetable oncogenes persisting through chemotherapy, providing rationale for future therapeutic approaches.