Objectives: Pseudomyxoma peritonei (PMP) is a rare, slow-growing cancer with few efficacious treatment options in unresectable cases. Mutations in the KRAS and GNAS oncogenes are common, but the reported frequencies vary greatly, most likely because of low tumor cellularity in peritoneal tumor samples. With treatments targeting these mutations becoming increasingly available, reliable detection of mutations is essential.
Methods: The frequency of KRAS and GNAS mutations was analyzed in tumor samples from 167 patients with verified PMP using targeted DNA sequencing and/or droplet digital polymerase chain reaction. When analysis of fresh-frozen peritoneal tumor samples did not reveal mutations, macrodissected formalin-fixed samples were analyzed.
Results: Mutations in cancer-related genes were detected in 98 % of the analyzed samples, with KRAS and GNAS mutated in 148 (89 %) and 139 (83 %) cases, respectively. In 48 % of the analyzed cases, the mutational diagnosis was based on primary tumor samples.
Conclusions: High frequencies of KRAS and GNAS mutations support the proposed role as driver mutations and as potential therapy targets. The primary tumor may serve as an alternative source of tumor material, increasing the likelihood of detecting targetable mutations. Combined with highly sensitive analytical methods, this approach facilitates selection of patients for novel targeted therapeutic strategies.
Keywords: GNAS mutation; KRAS mutation; oncogenes; pseudomyxoma peritonei; targeted therapy.
© 2025 the author(s), published by De Gruyter, Berlin/Boston.