title: Molecular profiles of high-grade and low-grade pseudomyxoma peritonei.
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.
authors.affiliation: Division of Clinical Genome Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Rei
authors.identifier: http://orcid.org/0000-0003-1180-2394
authors.initials: R
authors.lastname: Noguchi
authors.affiliation: Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yano
authors.affiliation: Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Gohda
authors.affiliation: Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Suda
authors.affiliation: Pathology Division of Clinical Laboratory, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Igari
authors.affiliation: Department of Pathology, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Ohta
authors.affiliation: Department of Advanced Medical Science, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Naohide
authors.initials: N
authors.lastname: Yamashita
authors.affiliation: Division of Clinical Genome Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Division of Clinical Genome Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Terakado
authors.affiliation: Division of Clinical Genome Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Ikenoue
authors.affiliation: Division of Clinical Genome Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Furukawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D011553:Pseudomyxoma Peritonei / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D059467:Transcriptome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016159:Tumor Suppressor Protein p53
keywords: DPAM; PMCA; TP53; mutation; pseudomyxoma peritonei