Heterozygous loss of NF2 is an early molecular alteration in well-differentiated papillary mesothelioma of the peritoneum

• Published in: Cancer genetics Vol. 205; no. 11; pp. 594 - 598
• Main Authors: Nemoto, Hiroshi, Tate, Genshu, Kishimoto, Koji, Saito, Mitsuo, Shirahata, Atsushi, Umemoto, Takehiro, Matsubara, Taketo, Goto, Tetsuhiro, Mizukami, Hiroki, Kigawa, Gaku, Mitsuya, Toshiyuki, Hibi, Kenji
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2012
• Subjects: Aged; Benign; DNA Mutational Analysis; E2F1; E2F1 Transcription Factor - genetics; Fatal Outcome; Female; Genes, Neurofibromatosis 2; Hematology, Oncology and Palliative Medicine; heterozygous loss; Histocytochemistry; Humans; Loss of Heterozygosity; Medical Education; mesothelioma; Mesothelioma - genetics; Mesothelioma - pathology; Mesothelioma - surgery; NF2; Peritoneal Neoplasms - genetics; Peritoneal Neoplasms - pathology; Polymorphism, Single Nucleotide; E2F1; NF2; mesothelioma; heterozygous loss
• ISSN: 2210-7762; 2210-7770
• DOI: 10.1016/j.cancergen.2012.08.005

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.