title: Heterozygous loss of NF2 is an early molecular alteration in well-differentiated papillary mesothelioma of the peritoneum.
abstract: Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare disease, and many cases are either benign neoplasms or low-graded malignancies; however, a few cases show rapid progressive clinical courses. No effective therapy has yet been established for WDPMP, and the molecular basis of WDPMP tumorigenesis has never been reported. This study shows the malignant transformation of WDPMP in a Japanese female patient, who was alive for 54 months after the initial diagnosis by a laparoscopic biopsy. A molecular analysis of single nucleotide polymorphisms (SNPs), which were located in the neurofibromatosis type 2 (NF2) gene, a tumor suppressor gene assigned to chromosome 22q12.3, revealed the loss of heterozygosity (LOH) of the NF2 gene. Furthermore, SNP analyses determined that LOH was observed in the IL17RA (22q11.1), CHECK2 (22q12.1), and SHANK3 (22q13.3) genes, thus suggesting that NF2 loss occurred through 22q deletions or monosomy 22. The LOH of the NF2 gene was observed in an early stage of WDPMP, thus indicating that LOH of the NF2 gene is an early molecular alteration, and NF2 loss is a molecular mechanism associated not only with malignant pleural mesothelioma, but also with WDPMP.
authors.affiliation: Department of Surgery, Showa University Fujigaoka Hospital, Yokohama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nemoto
authors.forename: Genshu
authors.initials: G
authors.lastname: Tate
authors.forename: Koji
authors.initials: K
authors.lastname: Kishimoto
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Saito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shirahata
authors.forename: Takehiro
authors.initials: T
authors.lastname: Umemoto
authors.forename: Taketo
authors.initials: T
authors.lastname: Matsubara
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Goto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mizukami
authors.forename: Gaku
authors.initials: G
authors.lastname: Kigawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Mitsuya
authors.forename: Kenji
authors.initials: K
authors.lastname: Hibi
mesh_terms: D000368:Aged; D004252:DNA Mutational Analysis; D050687:E2F1 Transcription Factor / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D016515:Genes, Neurofibromatosis 2; D006651:Histocytochemistry; D006801:Humans; D019656:Loss of Heterozygosity; D008654:Mesothelioma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human