Related Experiment Video
Updated: Mar 31, 2026
Culture and Imaging of Ex Vivo Organotypic Pseudomyxoma Peritonei Tumor Slices from Resected Human Tumor Specimens
Published on: December 9, 2022
Molecular profiles of high-grade and low-grade pseudomyxoma peritonei
Rei Noguchi1, Hideaki Yano2, Yoshimasa Gohda2
1Division of Clinical Genome Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Abstract:
Pseudomyxoma peritonei (PMP) is a rare disease exhibiting a distinct clinical feature caused by cancerous cells that produce mucinous fluid in the abdominal cavity. PMPs originate most frequently from the appendix and less frequently from the ovary. This disease can range from benign to malignant, and histologically, PMP is classified into two types: disseminated peritoneal adenomucinosis (DPAM) representing the milder phenotype, and peritoneal mucinous adenocarcinomas (PMCA) representing the aggressive phenotype. Although histological classification is clinically useful, the pathogenesis of PMP remains largely unknown. To elucidate the molecular mechanisms underlying PMP, we analyzed 18 PMP tumors comprising 10 DPAMs and 8 PMCAs. DNA was extracted from tumor and matched non-tumorous tissues, and was sequenced using Ion AmpliSeq Cancer Panel containing 50 cancer-related genes. Analysis of the data identified a total of 35 somatic mutations in 10 genes, and all mutations were judged as pathological mutations. Mutations were frequently identified in KRAS (14/18) and GNAS (8/18). Interestingly, TP53 mutations were found in three of the eight PMCAs, but not in the DPAMs. PIK3CA and AKT1 mutations were also identified in two PMCAs, but not in the DPAMs. These results suggested that KRAS and/or GNAS mutations are common genetic features of PMP, and that mutations in TP53 and/or genes related to the PI3K-AKT pathway may render malignant properties to PMP. These findings may be useful for the understanding of tumor characteristics, and facilitate the development of therapeutic strategies.
Insights
Pseudomyxoma peritonei (PMP) is a rare cancer. Genetic analysis revealed KRAS and GNAS mutations are common in PMP, while TP53 and PI3K-AKT pathway mutations indicate malignancy.
Area of Science:
- Oncology
- Genetics
- Gastroenterology
Background:
- Pseudomyxoma peritonei (PMP) is a rare condition characterized by mucinous fluid accumulation in the abdomen.
- PMP often originates from the appendix or ovary and presents with varying degrees of malignancy.
- The underlying pathogenesis of PMP remains poorly understood.
Purpose of the Study:
- To investigate the molecular mechanisms driving PMP development and progression.
- To identify common genetic mutations associated with PMP.
- To differentiate genetic profiles between benign and malignant PMP subtypes.
Main Methods:
- Analysis of 18 PMP tumors (10 DPAM, 8 PMCA) and matched non-tumorous tissues.
- DNA sequencing using the Ion AmpliSeq Cancer Panel (50 cancer-related genes).
- Identification and characterization of somatic mutations.
Main Results:
- Identified 35 somatic mutations in 10 genes across the PMP samples.
- KRAS mutations were frequent (14/18), as were GNAS mutations (8/18).
- TP53, PIK3CA, and AKT1 mutations were exclusively found in the aggressive PMCA subtype, not in DPAM.
Conclusions:
- KRAS and GNAS mutations are common genetic hallmarks of PMP.
- TP53 and PI3K-AKT pathway mutations are associated with the malignant phenotype of PMP.
- These genetic insights can aid in understanding PMP and developing targeted therapies.
