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

Our plain-English summary of Heterozygous loss of NF2 is an early molecular alteration in well-differentiated papillary mesothelioma of the peritoneum, by H. Nemoto, G. Tate, K. Kishimoto, et al (Cancer Genetics, 2012).

The study

• Authors: H. Nemoto, G. Tate, K. Kishimoto, M. Saito, A. Shirahata, T. Umemoto, T. Matsubara, T. Goto, H. Mizukami, G. Kigawa, T. Mitsuya, K. Hibi
• Journal: Cancer Genetics
• Published: 2012;205(11):594-8
• Type of article: Case report
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

Copyright © 2012 Elsevier Inc. All rights reserved.

In plain English

This report described one patient, a 73-year-old Japanese woman with well-differentiated papillary mesothelioma of the peritoneum (WDPMP), a rare tumor of the abdominal lining. A biopsied omental nodule was diagnosed as WDPMP; chemotherapy had no significant effects. A tumor mass removed about two years later showed increased cellular atypia, which the authors described as malignant progression. The patient died 54 months after treatment. The authors compared tumor DNA with a normal cervical sample. Three NF2 markers and markers in three other genes on chromosome 22's long arm showed loss of heterozygosity: two variants present in normal cells appeared as one in the tumor. The authors took this to suggest deletions of the long arm of chromosome 22 or loss of an entire chromosome 22. No mutation was found in the DNA binding region of the E2F1 gene. The authors reported that the NF2 loss was seen before malignant progression. They concluded that this suggested NF2 loss is an early event in WDPMP. The article did not report whether this patient had asbestos exposure. Its background section states that few WDPMPs arise in people with such exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Case report (brief communication) of one patient, with genetic analysis: tumor DNA was tested for loss of heterozygosity at SNP markers and for E2F1 mutations, using a normal cervical specimen as the comparison
• Who was studied: One 73-year-old Japanese woman seen at Showa University Fujigaoka Hospital, Yokohama, Japan. She was admitted for examination of ascites (fluid in the abdomen). Dates are not given.
• Exposure: The article does not report whether this patient was exposed to asbestos. The study examined genetic changes (NF2, chromosome 22q markers, E2F1) in her tumor. As background, the introduction states that few WDPMPs arise in patients with a history of asbestos exposure.
• Main results:
  • The laparoscopic biopsy of an omental nodule was diagnosed as WDPMP. The lining cells were positive for calretinin and negative for CEA.
  • Chemotherapy with paclitaxel (TXL) and irinotecan/cisplatin (CDDP) had no significant effects.
  • An omentum tumor mass was resected about 2 years after the initial biopsy.
  • In the resected tumor, histopathology showed increased cellular atypia, particularly in the stromal cells. The authors interpreted this as malignant progression.
  • The patient died 54 months after the treatment.
  • At the NF2 marker rs1008515, the normal cells showed two variants (cytosine and thymine), while the WDPMP showed only cytosine.
  • Two other NF2 markers, rs2267149 and rs2252472, also showed loss of heterozygosity. These data were not shown in the article.
  • Three markers in the IL17RA, CHEK2 (written CHECK2 in places) and SHANK3 genes, all on the long arm of chromosome 22, showed loss of heterozygosity in the tumor.
  • The authors interpreted the chromosome 22 findings as indicating that NF2 loss was caused by deletions of the long arm of chromosome 22 (22q hemizygous deletions) or loss of a whole chromosome 22 (monosomy 22).
  • No mutation was found in the E2F1 gene, either at R166 or in the DNA binding domain. These data were not shown in the article.
  • The authors reported that loss of heterozygosity of NF2 was observed in the WDPMP before malignant progression.
• The authors' conclusion: The authors concluded that this first reported case of a WDPMP with heterozygous loss of NF2 suggested that loss of heterozygosity of the NF2 gene is an early molecular event in WDPMP.
• Limitations the authors state:
  • The authors stated that further analyses are necessary to determine whether R166H is a mutational hot spot in WDPMP.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Well-Differentiated Papillary Mesothelioma, Peritoneum, Neoplasm, Carcinogenesis, Malignant Transformation, Biopsy, Tumor Suppressor Gene, Pleural Mesothelioma.

Related studies

• First somatic mutation of E2F1 in a critical DNA binding residue discovered in well-differentiated papillary mesothelioma of the peritoneum — W. Yu, W. Chan-On, et al. (2011)
• Well-differentiated papillary mesothelioma of the peritoneum is genetically defined by mutually exclusive mutations in TRAF7 and CDC42 — M. Stevers, J.T. Rabban, et al. (2019)
• Well-differentiated papillary mesothelioma of the female peritoneum: a clinicopathologic study of 26 cases — A. Malpica, S. Sant'Ambrogio, et al. (2012)
• Well-differentiated papillary mesothelioma of the peritoneum: a pathological analysis and review of the literature — A.V. Hoekstra, M.W. Riben, et al. (2005)
• Well-differentiated papillary mesothelioma of the peritoneum: a separate entity — K. Hoekman, G. Tognon, et al. (1996)
• Therapeutic strategies for well-differentiated papillary mesothelioma of the peritoneum — Y.K. Lee, H.J. Jun, et al. (2013)

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