The mutational landscape of upper gastrointestinal adenocarcinomas- A study of similarities and differences

The gastrointestinal tract is home to a wide variety of neoplasms. Gastrointestinal adenocarcinomas display distinct prognostic patterns. With the advent of next generation sequencing, attempts are being made to delineate distinct molecular characteristics of these adenocarcinomas from adjoining anatomical sites.

Thirty-seven cases of upper gastrointestinal adenocarcinomas including those of the esophagus, gastroesophageal junction, stomach, small intestine and gallbladder were retrieved. Next generation sequencing data consisting of base substitutions, copy number variations, indels and rearrangements, in 324 genes, were analyzed for recurrent genetic abnormalities. Statistical analysis was performed using IBM SPSS25 and SAS software.

Genetic alterations were found in 181 genes. APC mutations were found in 50% of the esophageal adenocarcinomas, 5% of the gastric adenocarcinomas and 33.3% of the small intestinal adenocarcinomas (p = 0.04). PIK3 gene family mutations were found in 10% of the gastric adenocarcinomas, 66% of the gall bladder adenocarcinomas and 66% of the small intestinal adenocarcinomas (p = 0.002). The mutations were found exclusively in the PIK3 class 1 family. TP53 mutations were more common in tumors with intact DNA mismatch repair protein expression as assessed by immunohistochemistry (p = 0.042).

In this study, APC gene mutations were found to be more frequent in esophageal and small intestinal adenocarcinomas than previously reported. PIK3 class 1 gene family mutations were found to be more frequent in gallbladder and small intestinal adenocarcinomas. An inverse relationship was found between TP53 mutations and loss of DNA mismatch repair protein expression.