by ecancer reporter Janet Fricker

In a sequencing study 26 genes have been identified as being significantly mutated in patients with oesophageal adenocarcinoma, (OAC) reports a US study published online in “Nature Genetics”. The identification of the genes, write the authors, has the potential to provide a “road map” for the development of new treatments.

Over the last 30 years the incidence of OAC in Western countries has risen six fold, with increases attributed to rising rates of gastroesophageal reflux disease (GERD), Barrett’s oesophagus and obesity. With five year survival rates of just 15% there is great urgency to elucidate the genomic alterations underlying OAC to enhance understanding of these tumours, aid in early diagnosis and identify new therapeutic targets. Limited knowledge of the genomic aberrations underlying OAC has undoubtedly hindered the development of new therapies.

Adam Bass and colleagues, from Dana Farber Cancer Institute, Boston, MA, report on their study sequencing the coding regions of 149 OAC tumours and matched normal tissue, and furthermore undertaking whole genome sequencing for 15 of these pairs.

Altogether the team identified 26 significantly mutated genes, of which five genes (TP53, CDKN2A, SMAD4, ARID1A and PIK3CA) had previously been implicated in OAC. The newly identified significantly mutated genes included chromatin-modifying factors and candidate contributors SPG20, TLR4, ELMO1 and DOCK2.

“This mutational spectrum seems to be unique to EAC[OAC], suggesting that these mutations are attributable to gastroesophaeal reflux, where the gastric and duodenal contents travel into the lower esophagus, creating an environment of inflammation,” write the authors.

With 23% of the mutations identified having inhibitors that are either in preclinical development or clinical use the outlook is promising. “These data provide an enhanced road map for the study of EAC and the much-needed development of new therapies for this deadly cancer,” write the authors.

Reference

A Dulak, P Stojanov, S Peng, et al. Exome and whole genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nature Genetics. Doi:10.1038/ng.2591.