DAXX is associated with early recurrence of pancreatic neuroendocrine tumors after R0 resection

Benjamin C Greenspun ¹, Amanda Foshag ², Abhinay Tumati ²

⁰Department of Surgery, Weill Cornell Medicine, New York, NY; Center for Genomic Health, Weill Cornell Medicine, New York, NY.

Surgery +

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October 4, 2024

View abstract on PubMed

Summary

DAXX mutations are linked to pancreatic neuroendocrine tumor recurrence and mortality after surgery. These findings highlight DAXX as a potential biomarker for aggressive disease, guiding future treatment strategies.

Area Of Science

Oncology
Genetics
Surgical Pathology

Background

Mutations in ATRX, DAXX, MEN1, and PTEN are implicated in pancreatic neuroendocrine tumor (PNET) development.
The prognostic value of these mutations, particularly after curative-intent surgery (R0 resection), requires further clarification.

Purpose Of The Study

To identify genomic signatures associated with PNET disease-specific mortality and recurrence post-R0 resection.
To evaluate the clinical utility of specific gene mutations as prognostic markers in PNETs.

Main Methods

Whole exome sequencing was performed on PNET patients with available survival data obtained from cBioPortal.
Clinicopathologic variables, genomic data, and patient outcomes were analyzed to identify correlations.

Main Results

DAXX mutations were significantly more frequent in the recurrent cohort (36% vs. 11%) and associated with vascular invasion.
Higher tumor mutation burden was observed in patients with recurrent disease.
Recurrent PNETs exhibited larger tumor size, increased vascular invasion, lymph node positivity, and metastatic disease compared to the disease-free cohort.

Conclusions

DAXX mutations demonstrate prognostic significance following curative-intent surgery for PNETs.
Further research is warranted to explore DAXX mutations as a biomarker for identifying aggressive PNET features and guiding therapeutic decisions.