Pancreatic neuroendocrine tumor pathophysiology

DNA mutation analysis in well-differentiated pancreatic neuroendocrine tumors identified four important findings:^[1][2]

• as expected, the genes mutated in NETs, MEN1, ATRX, DAXX, TSC2, PTEN and PIK3CA,^[1] are different from the mutated genes previously found in pancreatic adenocarcinoma.^[3][4]

• one in six well-differentiated pancreatic NETs have mutations in mTOR pathway genes, such as TSC2, PTEN and PIK3CA.^[1] The sequencing discovery might allow selection of which NETs would benefit from mTOR inhibition such as with everolimus, but this awaits validation in a clinical trial.

• mutations affecting a new cancer pathway involving ATRX and DAXX genes were found in about 40% of pancreatic NETs.^[1] The proteins encoded by ATRX and DAXX participate in chromatin remodeling of telomeres; these mutations are associated with a telomerase-independent maintenance mechanism termed ALT (alternative lengthening of telomeres) that results in abnormally long telomeric ends of chromosomes.

• ATRX/DAXX and MEN1 mutations were associated with a better prognosis.^[1]