In the literature: October 2016

Abstract

A consortium on clinical and molecular stratification on oesophageal adenocarcinoma established in Britain has recently published in Nature Genetics , a whole-genomic sequencing analysis of more than 100 samples.1 Interestingly, they describe three distinct molecular subtypes with potential treatment relevance. This observation has also been verified in an independent validation cohort. Those three types are: (1) the ones showing homologous recombination and chromosome segregation pathways defects with enrichment of a BRCA signature. These tumours would be sensitive to DNA damaging agents, including neutron and photon irradiation with the addition of PARP inhibitors, (2) a group with high mutational load and neoantigen burden, associated with an increased CD8+ T-cell density and with a dominant T>G mutational pattern, in which immunotherapy with anti-PD1 or PDL1 antibodies could have a role and (3) evidence of an ageing imprint with a C>A/T pattern and fewer unstable genomes and large duplication events, which may be sensitive to chemotherapy and antiHER2 or MET directed therapies. The clinical characteristics of the three subgroups did not differ significantly, implying that the classification, and hence spectrum of mutation patterns, does not vary with smoking, age, sex, tumour histopathological grade, tumour stage, response to chemotherapy, overall or recurrence-free survival, etc. Therefore, the mutation signature profiles seem to be …