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

Nemoto, Hiroshi; Tate, Genshu; Kishimoto, Kenji; Shimada, Mitsuo; Shirahata, Atsushi; Umemoto, Takehiro; Matsubara, Taketo; Goto, Tetsuhiro; Mizukami, Hajime; Kigawa, Gaku; Mitsuya, Toshiyuki; Hibi, Kenji

doi:10.1016/j.cancergen.2012.08.005

Cited by 23 publications

(14 citation statements)

References 22 publications

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“…Recently, heterozygous loss of NF2 has been reported to be observed in a malignant transformed case of well-differentiated papillary mesothelioma of the peritoneum (WDPMP), thus indicating that the loss of heterozygosity of the NF2 gene is an early molecular alteration in malignant pleural mesothelioma and also in WDPMP 30. In our study, deletion of 22q12 showed no significant difference between peritoneal and pleural MM.…”

Section: Discussionsupporting

confidence: 40%

Comparison of genomic abnormality in malignant mesothelioma by the site of origin

et al. 2014

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Section: Discussionsupporting

confidence: 40%

Comparison of genomic abnormality in malignant mesothelioma by the site of origin

et al. 2014

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“…The tumor suppressor neurofibromin 2 is encoded by the NF2 gene, located on chromosome 22q12. Mutations in NF2 are found in ~40% of MPMs, and heterozygous loss of NF2 is identified in ~74% of MPMs (6,7). Mutations are rare in the TP53 and RAS genes, which are frequently present in epithelial solid tumors (8,9).…”

Section: Introductionmentioning

confidence: 99%

DNA copy number gains in malignant pleural mesothelioma

et al. 2015

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Abstract. Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with an extremely poor prognosis. The incidence of MPM is increasing as a result of widespread exposure to asbestos. The molecular pathogenesis of MPM remains unclear. The present study analyzed the frequency of various genomic copy number gains (CNGs) in MPM using reverse transcription-quantitative polymerase chain reaction. A total of 83 primary MPMs and 53 primary lung adenocarcinomas were analyzed to compare the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2. In MPM, the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2 were detected in 12 (14.5%), 8 (9.6%), 5 (6.0%), 4 (4.8%) and 1 (1.2%) of the samples, respectively. In lung adenocarcinomas, the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2 were detected in 21 (39.6%), 12 (22.6%), 5 (9.4%), 10 (18.9%) and 0 (0.0%) of the samples, respectively. The CNGs of EGFR, KRAS and FGFR1 were significantly less frequent in the MPMs compared with the lung adenocarcinomas (P=0.0018, 0.048 and 0.018, respectively). Overall, the MPMs exhibited these CNGs less frequently compared with the lung adenocarcinomas (P=0.0002). The differences in CNGs between the two tumor types suggested that they are genetically different. IntroductionMalignant pleural mesothelioma (MPM) is a tumor derived from the mesothelial cells lining the pleural spaces. MPM has highly invasive and aggressive clinical characteristics. Approximately 80% of MPM patients have a history of occupational asbestos exposure, which is considered to be a risk factor for the development of the disease (1). The molecular pathogenesis of MPM is not well understood. The most common mutations in MPMs are losses in 9p21, 1p36, 14q32 and 22q12, and gains in 5p, 7p and 8q24, which have been detected by comparative genomic hybridization analysis (2,3). Homozygous deletion of the 9p21 locus encoding two critical cyclin-dependent kinase inhibitors, p16INK4a and p15 INK4b , have been reported in up to 80% of MPMs, and this mutation may be of diagnostic utility (4,5). The tumor suppressor neurofibromin 2 is encoded by the NF2 gene, located on chromosome 22q12. Mutations in NF2 are found in ~40% of MPMs, and heterozygous loss of NF2 is identified in ~74% of MPMs (6,7). Mutations are rare in the TP53 and RAS genes, which are frequently present in epithelial solid tumors (8,9). Epigenetic alterations, such as DNA methylation, have been found in MPMs, which have a different profile compared with lung cancer (10-12). MPMs, particularly of the epithelioid subtype, may be hard to differentiate from adenocarcinoma arising in the lung periphery, and epidemiological evidence indicates that asbestos and smoking are shared risk factors for these diseases (2,13,14). Currently, the differential diagnosis of MM is based on a range of morphological analyses, including a combination of histological and immunohistochemical staining, and electron microscopy (13,15,16).Cytogenetic studies have been performed on MPMs and adenocarcinomas arising in the lung periphery, however, no chromosomal aberra...

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“…[89] At the molecular level neurofibromatosis 2 (NF2) gene alterations have been associated with this tumor. [90] In FNA cytology one can appreciate the uniformity of cells distributed in tubule-papillary clusters. [91] However, the mesothelial cells of WDPM in fluids can occur singly in addition to forming papillary clusters [Figure 17].…”

Section: Introductionmentioning

confidence: 99%

Abdominopelvic washings: A comprehensive review

Rodrı́guez¹,

Khalbuss²,

Austin³

et al. 2013

CytoJournal

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Intraperitoneal spread may occur with gynecological epithelial neoplasms, as well as with non-gynecological malignancies, which may result in serosal involvement with or without concomitant effusion. Therefore, washings in patients with abdominopelvic tumors represent important specimens for cytologic examination. They are primarily utilized for staging ovarian cancers, although their role has decreased in staging of endometrial and cervical carcinoma. Abdominopelvic washings can be positive in a variety of pathologic conditions, including benign conditions, borderline neoplastic tumors, locally invasive tumors, or distant metastases. In a subset of cases, washings can be diagnostically challenging due to the presence of co-existing benign cells (e.g., mesothelial hyperplasia, endosalpingiosis, or endometriosis), lesions in which there is only minimal atypia (e.g., serous borderline tumors) or scant atypical cells, and the rarity of specific tumor types (e.g., mesothelioma). Ancillary studies including immunocytochemistry and fluorescence in situ hybridization may be required in difficult cases to resolve the diagnosis. This article provides a comprehensive and contemporary review of abdominopelvic washings in the evaluation of gynecologic and non-gynecologic tumors, including primary peritoneal and mesothelial entities.

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

Cited by 23 publications

References 22 publications

Comparison of genomic abnormality in malignant mesothelioma by the site of origin

Comparison of genomic abnormality in malignant mesothelioma by the site of origin

DNA copy number gains in malignant pleural mesothelioma

Abdominopelvic washings: A comprehensive review

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