Molecular profiles of high‐grade and low‐grade pseudomyxoma peritonei

Cancer Medicine

Rei Noguchi⁵  Hideaki Yano²  Yoshimasa Gohda²  Ryuichiro Suda²  Toru Igari³  Yasunori Ohta¹  Naohide Yamashita⁶  Kiyoshi Yamaguchi⁴  Yumi Terakado⁴  Tsuneo Ikenoue⁴ 

[1] Department of Pathology, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan;Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan;Pathology Division of Clinical Laboratory, National Center for Global Health and Medicine, Tokyo, Japan;Division of Clinical Genome Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan;ORCID:orcid.org/0000-0003-1180-2394;Department of Advanced Medical Science, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

关键词: DPAM;    mutation;    PMCA;    pseudomyxoma peritonei;    TP53;   

DOI  :  10.1002/cam4.542

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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