Loss of DAXX and ATRX are associated with chromosome instability and reduced survival of patients with pancreatic NETS (Gastroenterology, 21 October 2013)

Malignant pancreatic neuroendocrine tumours (pNETs) are characterised by chromosomal instability. However, the underlying cause for this remains unclear. Recent studies from a laboratory in John Hopkins demonstrated, using whole exome sequencing, that mutations in DAXX (Death domain associated protein gene) and ATRX (ATR-X gene) are frequently present. The mutations in ATRX and DAXX were found to be mutually exclusive. The importance of the presence or absence of these mutations has not previously been clearly determined.

This study examined expression DAXX and ATRX in 142 samples, of which results were obtained for 92 patients with pNETs. Further sequencing was performed in 25 patients in whom frozen tissue was available, a further 9 new mutations were identified in DAXX and 3 in ATRX.

The researchers determined prognostic significance by assessing DAXX and ATRX expression in an additional series of 70 patients. This demonstrated that the loss of DAXX or ATRX is associated with chromosomal instability. More importantly, they also demonstrated that loss of DAXX or ATRX was associated with shorter survival. They concluded that DAXX and ATRX negative tumours are an aggressive subset of pNETs.

Source: Gastroenterology (published study)