Genetic mutations of appendix cancer identified, may impact treatment

To understand why some patients with appendix cancer respond to standard treatment while others do not, University of California San Diego (UC San Diego) School of Medicine and Moores Cancer Center researchers, in collaboration with Foundation Medicine, performed genetic profiling on 703 appendiceal tumours — the largest such study of this disease to date — to compare mutations present in both cancer types.

The findings, published online 8 August in JCO Precision Oncology, confirm that genetic mutations in appendix cancer are distinct from those found in colon cancer and that mutations in the genes TP53 and GNAS are good predictors of survival among people with appendix cancer.

"For tumours that are rare like appendix cancer, obtaining molecular profiles will help identify potential treatment options since we don't have the clinical trial data to help guide treatments as we do in common tumours," says lead author John Paul Shen, MD, a postdoctoral fellow in the lab of co-author Trey Ideker, PhD, University of California at San Diego School of Medicine professor of medicine. "Equally important, the mutation profile can be used as a biomarker to separate high-risk patients, who need intensive treatment, from low-risk patients who may not need such an intensive treatment."

The retrospective study found that appendix cancer is comprised of five distinct subtypes: mucinous adenocarcinomas (46 per cent), adenocarcinomas (30 per cent), goblet cell carcinoids (12 per cent), pseudomyxoma peritonei (7.7 per cent) and signet ring cell carcinomas (5.2 per cent).

A mutation in the gene GNAS, rare in colon cancer, was found to be quite frequent in appendix cancer, especially in mucinous adenocarcinomas (52 per cent) and pseudomyxoma peritonei (72 per cent). Patients with tumours harboring a GNAS mutation had a median survival of almost 10 years, while those whose tumours had a TP53 mutation had median survival of only three years. Patients who had neither gene mutation had a six-year median survival rate.

"This striking finding raises the question of whether patients with early stage, GNAS-mutant tumours need to be treated with chemotherapy, as it is possible they could be cured with surgery alone; a question we will focus on in our next study," said Shen.

"Understanding the molecular differences between the subtypes of appendiceal tumors is an important stepping stone for future clinical trials to develop and test different therapeutic approaches that are specific to this disease," said senior author Olivier Harismendy, PhD, assistant professor of medicine at UC San Diego Moores Cancer Center.