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

Takeda, Maiko; Kasai, Takahiko; Enomoto, Yasunori; Takano, Mitsuo; Morita, Kenichi; Nakai, Tokiko; Iizuka, Norishige; Maruyama, Hiroshi; Ohbayashi, Chiho

doi:10.1136/jclinpath-2014-202465

Cited by 20 publications

(11 citation statements)

References 28 publications

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“…There also appear to be molecular differences between pleural and peritoneal mesothelioma cells in genomic copy number losses and gains, indicating that different genetic pathways may be implicated at the different site. 79,125 However, there are no data thus far that would suggest specific etiologies associated with 1 or any combination of these mutations/deletions.…”

Section: Spontaneous (Idiopathic) Mesotheliomasmentioning

confidence: 99%

Malignant Mesothelioma and Its Non-Asbestos Causes

Attanoos

Churg

Galateau-Salle

et al. 2018

Archives of Pathology & Laboratory Medicine

177

129

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- Currently, most pleural mesotheliomas (70% to 90%) in men in Europe and North America are attributable to asbestos exposure; for peritoneal mesothelioma the proportion is lower. In North America few mesotheliomas in women at any site are attributable to asbestos exposure, but in Europe the proportion is higher and varies considerably by locale. In certain geographic locations other types of mineral fibers (erionite, fluoro-edenite, and probably balangeroite) can induce mesothelioma. Therapeutic radiation for other malignancies is a well-established cause of mesothelioma, with relative risks as high as 30. Carbon nanotubes can also induce mesotheliomas in animals but there are no human epidemiologic data that shed light on this issue. Chronic pleural inflammation may be a cause of mesothelioma but the data are scanty. Although SV40 can induce mesotheliomas in animals, in humans the epidemiologic data are against a causative role. A small number of mesotheliomas (probably in the order of 1%) are caused by germline mutations/deletions of BRCA1-associated protein-1 ( BAP1) in kindreds that also develop a variety of other cancers. All of these alternative etiologies account for a small proportion of tumors, and most mesotheliomas not clearly attributable to asbestos exposure are spontaneous (idiopathic).

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Section: Spontaneous (Idiopathic) Mesotheliomasmentioning

confidence: 99%

Malignant Mesothelioma and Its Non-Asbestos Causes

Attanoos

Churg

Galateau-Salle

et al. 2018

Archives of Pathology & Laboratory Medicine

177

129

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“…The genetic alterations that drive mesotheliomas occur at distinct frequencies depending on the anatomic origin of the tumor. One study revealed chromosome 9p21 deletion more frequently in pleural than in peritoneal tumors (85% vs. 36%), whereas 5p15 and 7p12 gains were more common in peritoneal than in pleural tumors [ 39 ].…”

Section: Genomic Profiling Of Mpmmentioning

confidence: 99%

Malignant peritoneal mesothelioma: clinical aspects, and therapeutic perspectives

Boussios

Moschetta

Karathanasi

et al. 2018

aog

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Malignant peritoneal mesothelioma (MPM) is a rare disease with a wide clinical spectrum. It arises from the peritoneal lining and commonly presents with diffuse, extensive spread throughout the abdomen and, more rarely, metastatic spread beyond the abdominal cavity. Computed tomography, magnetic resonance imaging and positron-emission tomography are important diagnostic tools used for the preoperative staging of MPM. The definitive diagnosis is based on histopathological analysis, mainly via immunohistochemistry. In this regard, paired-box gene 8 negativity represents a useful diagnostic biomarker for differentiating MPM from ovarian carcinoma. In addition, BRCA1-associated protein-1 (BAP1) loss is specific to MPM and allows it to be distinguished from both benign mesothelial lesions and ovarian serous tumors. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has become an increasingly important therapeutic approach, while systemic therapies are still being developed. Histology, Ki-67, completeness of cytoreduction, age, sex, and baseline thrombocytosis are commonly used to optimize patient selection for CRS with HIPEC. Additionally, it is well recognized that, compared to other subtypes, an epithelial morphology is associated with a favorable prognosis, whereas baseline thrombocytosis predicts an aggressive biologicalbehavior. Platelets and other immunologic cytokines have been evaluated as potential novel therapeutic targets. Epigenetic modifiers, including BAP1, SETD2 and DDX3X, are crucial in mesothelial tumorigenesis and provide opportunities for targeted treatment. Overexpression of the closely interacting phosphoinositide 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) pathways appears crucial in regulation of the malignant phenotype. The use of targeted therapies with PI3K-mTOR-based inhibitors requires further clinical assessment as a novel approach.

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“…Indeed, one study performed FISH on mesotheliomas from different sites of origin and found chromosome 9p21 deletion much more commonly in pleural than peritoneal tumors (85% versus 36%), whereas 5p15 and 7p12 gains were more common in peritoneal than pleural tumors. 15 A recent genome-wide analysis of 12 peritoneal mesotheliomas found BAP1 alterations (either deletions or truncating mutations) in 7 cases, but failed to identify alterations in CDKN2A or NF2 that are common in pleural mesotheliomas. 16 Another recent study correlating genetic status with outcomes for patients with peritoneal mesothelioma identified frequent loss of BAP1 immunostaining that did not correlate with significant differences in outcome, but did find that tumors harboring both CDKN2A homozygous deletion and NF2 hemizygous loss were associated with worse progression-free and overall survival.…”

Section: Introductionmentioning

confidence: 99%

Genomic profiling of malignant peritoneal mesothelioma reveals recurrent alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X

Joseph

Chen

Nasr³

et al. 2017

Modern Pathology

102

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Malignant mesothelioma is a rare cancer that arises from the mesothelial cells that line the pleural cavity and less commonly from the peritoneal lining of the abdomen and pelvis. Most pleural mesotheliomas arise in patients with a history of asbestos exposure, whereas the association of peritoneal mesotheliomas with exposure to asbestos and other potential carcinogens is less clear, suggesting that the genetic alterations which drive malignant peritoneal mesothelioma may be unique from those in pleural mesothelioma. Treatment options for all malignant mesotheliomas are currently limited, with no known targeted therapies available. To better understand the molecular pathogenesis of malignant peritoneal mesothelioma, we sequenced 510 cancer-related genes in 13 patients with malignant mesothelioma arising in the peritoneal cavity. The most frequent genetic alteration was biallelic inactivation of the BAP1 gene, which occurred in 9/13 cases, with an additional 2 cases demonstrating monoallelic loss of BAP1. All 11 of these cases demonstrated loss of BAP1 nuclear staining by immunohistochemistry, whereas the 2 tumors without BAP1 alteration and all 42 cases of histologic mimics in peritoneum (8 multilocular peritoneal inclusion cyst, 6 well-differentiated papillary mesothelioma of the peritoneum, 16 adenomatoid tumor, and 12 low-grade serous carcinoma of the ovary) demonstrated intact BAP1 nuclear staining. Additional recurrently mutated genes in this cohort of malignant peritoneal mesotheliomas included NF2 (3/13), SETD2 (2/13), and DDX3X (2/13). While these genes are known to be recurrently mutated in pleural mesotheliomas, the frequencies are distinct in peritoneal mesotheliomas, with nearly 85% of peritoneal tumors harboring BAP1 alterations versus only 20-30% of pleural tumors. Together, these findings demonstrate the importance of epigenetic modifiers including BAP1, SETD2, and DDX3X in mesothelial tumorigenesis and suggest opportunities for targeted therapies.

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

Cited by 20 publications

References 28 publications

Malignant Mesothelioma and Its Non-Asbestos Causes

Malignant Mesothelioma and Its Non-Asbestos Causes

Malignant peritoneal mesothelioma: clinical aspects, and therapeutic perspectives

Genomic profiling of malignant peritoneal mesothelioma reveals recurrent alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X

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