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Archives of Pathology & Laboratory... May 2024Molecular testing has increasingly been utilized in the evaluation of mesothelioma. Diffuse mesothelioma comprises multiple distinct genetic subgroups. While most... (Review)
Review
CONTEXT.—
Molecular testing has increasingly been utilized in the evaluation of mesothelioma. Diffuse mesothelioma comprises multiple distinct genetic subgroups. While most diffuse mesotheliomas lack oncogenic kinase mutations and instead harbor alterations involving tumor suppressors and chromatin regulators, a minor subset of tumors is characterized by uncommon alterations such as germline mutations, genomic near-haploidization, ALK rearrangement, ATF1 rearrangement, or EWSR1::YY1 fusion.
OBJECTIVE.—
To provide updates on the salient molecular features of diffuse mesothelioma, mesothelioma in situ, and other mesothelial lesions: well-differentiated papillary mesothelial tumor, adenomatoid tumor, peritoneal inclusion cyst, and others. We consider the diagnostic, prognostic, and predictive utility of molecular testing in mesothelial lesions.
DATA SOURCES.—
We performed a literature review of recently described genetic features, molecular approaches, and immunohistochemical tools, including BAP1, MTAP, and merlin in mesothelioma and other mesothelial lesions.
CONCLUSIONS.—
Our evolving understanding of the molecular diversity of diffuse mesothelioma and other mesothelial lesions has led to considerable changes in pathology diagnostic practice, including the application of immunohistochemical markers such as BAP1, MTAP, and merlin (NF2), which are surrogates of mutation status. In young patients and/or those without significant asbestos exposure, unusual mesothelioma genetics such as germline mutations, ALK rearrangement, and ATF1 rearrangement should be considered.
Topics: Humans; Mesothelioma; Immunohistochemistry; Biomarkers, Tumor; Neoplasms, Mesothelial; Mesothelioma, Malignant; Mutation; Tumor Suppressor Proteins; Ubiquitin Thiolesterase
PubMed: 38190277
DOI: 10.5858/arpa.2023-0213-RA -
Thoracic Cancer Sep 2023Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the pleura, and its incidence has been increasing in recent years. Due to the insidious onset...
Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the pleura, and its incidence has been increasing in recent years. Due to the insidious onset and strong local invasiveness of MPM, most patients are diagnosed in the late stage and early screening and treatment for high-risk populations are crucial. The treatment of MPM mainly includes surgery, chemotherapy, and radiotherapy. Immunotherapy and electric field therapy have also been applied, leading to further improvements in patient survival. The Mesothelioma Group of the Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) developed a national consensus on the clinical diagnosis and treatment of MPM based on existing clinical research evidence and the opinions of national experts. This consensus aims to promote the homogenization and standardization of MPM diagnosis and treatment in China, covering epidemiology, diagnosis, treatment, and follow-up.
Topics: Humans; Consensus; East Asian People; Mesothelioma, Malignant; Pleural Neoplasms; China
PubMed: 37461124
DOI: 10.1111/1759-7714.15022 -
Journal of Thoracic Oncology : Official... Jul 2017Although the association between exposure to asbestos and malignant mesothelioma (particularly malignant pleural mesothelioma) has been well established, the health... (Review)
Review
Although the association between exposure to asbestos and malignant mesothelioma (particularly malignant pleural mesothelioma) has been well established, the health impact of environmental exposure (EE) to asbestos has been less studied. This review summarizes the most recent studies on the association between malignant mesothelioma and EE with asbestos to identify features associated with EE and quantify the association with malignant mesothelioma. There were 44 studies from 18 countries that met our selection criteria, with a considerable amount of heterogeneity in their study design, measures of exposure, and health outcomes. The male-to-female ratio was close to or less than 1 and generally lower than the ratio reported when both occupational and environmental exposures were considered. Although recent studies have continued to improve our understanding of environmental exposure to asbestos, challenges remain. We have highlighted a few new research directions, such as a need for reliable matrices to identify common and less recognized types of EE, asbestos biomarker studies specifically focusing on EE, and research on populations and geographic areas that have not been previously studied.
Topics: Asbestos; Environmental Exposure; Female; Humans; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant
PubMed: 28412495
DOI: 10.1016/j.jtho.2017.04.002 -
Journal of Translational Medicine Oct 2023Mesothelioma is a cancer typically caused by asbestos. Mechanistically, asbestos carcinogenesis has been linked to the asbestos-induced release of HMGB1 from the nucleus... (Review)
Review
Mesothelioma is a cancer typically caused by asbestos. Mechanistically, asbestos carcinogenesis has been linked to the asbestos-induced release of HMGB1 from the nucleus to the cytoplasm, where HMGB1 promotes autophagy and cell survival, and to the extracellular space where HMGB1 promotes chronic inflammation and mesothelioma growth. Targeting HMGB1 inhibited asbestos carcinogenesis and the growth of mesothelioma. It is hoped that targeting HMGB1 will be a novel therapeutic strategy that benefits mesothelioma patients. Severe restrictions and/or a complete ban on the use of asbestos were introduced in the 80 and early 90s in the Western world. These measures have proven effective as the incidence of mesothelioma/per 100,000 persons is decreasing in these countries. However, the overall number of mesotheliomas in the Western world has not significantly decreased. There are several reasons for that which are discussed here: (1) the presence of asbestos in old constructions; (2) the development of rural areas containing asbestos or other carcinogenic mineral fibers in the terrain; (3) the discovery of an increasing fraction of mesotheliomas caused by germline genetic mutations of BAP1 and other tumor suppressor genes; (4) mesotheliomas caused by radiation therapy; (5) the overall increase in the population and of the fraction of older people who are much more susceptible to develop all types of cancers, including mesothelioma. In summary, the epidemiology of mesothelioma is changing, the ban on asbestos worked, there are opportunities to help mesothelioma patients especially those who develop in a background of germline mutations and there is the opportunity to prevent a mesothelioma epidemic in the developing world, where the use of asbestos is increasing exponentially. We hope that restrictive measures similar to those introduced in the Western world will soon be introduced in developing countries to prevent a mesothelioma epidemic.
Topics: Humans; Asbestos; Carcinogenesis; HMGB1 Protein; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Tumor Suppressor Proteins; Ubiquitin Thiolesterase
PubMed: 37880686
DOI: 10.1186/s12967-023-04614-5 -
Journal of Thoracic Oncology : Official... Sep 2018Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that arises from the mesothelial surface of the pleural and peritoneal cavities, the pericardium,... (Review)
Review
Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that arises from the mesothelial surface of the pleural and peritoneal cavities, the pericardium, and rarely, the tunica vaginalis. The incidence of MPM is expected to increase worldwide in the next two decades. However, even with the use of multimodality treatment, MPM remains challenging to treat, with a 5-year survival rate of less than 5%. The International Association for the Study of Lung Cancer has gathered experts in different areas of mesothelioma research and management to summarize the most significant scientific advances and new frontiers related to mesothelioma therapeutics.
Topics: Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant
PubMed: 29966799
DOI: 10.1016/j.jtho.2018.06.011 -
Expert Opinion on Drug Discovery Jun 2021Mesothelioma is an aggressive mesothelial lining tumor. Available drug therapies include chemotherapeutic agents, targeted molecular therapies, and immune system... (Review)
Review
INTRODUCTION
Mesothelioma is an aggressive mesothelial lining tumor. Available drug therapies include chemotherapeutic agents, targeted molecular therapies, and immune system modulators. Mouse models were instrumental in the discovery and evaluation of such therapies, but there is need for improved understanding of the role of inflammation, tumor heterogeneity, mechanisms of carcinogenesis, and the tumor microenvironment. Novel mouse models may provide new insights and drive drug therapy discovery that improves efficacy.
AREAS COVERED
This review concerns available mouse models for mesothelioma drug discovery and development including the advantages and disadvantages of each. Gaps in current knowledge of mesothelioma are highlighted, and future directions for mouse model research are considered.
EXPERT OPINION
Soon, CRISPR-Cas gene-editing will improve understanding of mesothelioma mechanisms foundational to the discovery and testing of efficacious therapeutic targets. There are at least two likely areas of upcoming methodology development. One is concerned with precise modeling of inflammation - is it a causal process whereby inflammatory signals contribute to tumor initiation, or is it a secondary passenger process driven by asbestos exposure effects? The other area of methods improvement regards the availability of humanized immunocompromised mice harboring patient-derived xenografts. Combining human tumors in an environment with human immune cells will enable rapid innovation in immuno-oncology therapeutics.
Topics: Animals; Asbestos; Carcinogenesis; Drug Discovery; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Mice; Tumor Microenvironment
PubMed: 33380218
DOI: 10.1080/17460441.2021.1867530 -
The Journal of Thoracic and... Jun 2022
Topics: Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Reference Standards
PubMed: 34600767
DOI: 10.1016/j.jtcvs.2021.08.077 -
Frontiers in Immunology 2023
Topics: Humans; Mesothelioma, Malignant; Mesothelioma; Pleural Neoplasms; Immunotherapy
PubMed: 37554331
DOI: 10.3389/fimmu.2023.1251384 -
ESMO Open Mar 2020Malignant pleural mesothelioma is a rare and aggressive malignancy mostly associated with occupational asbestos exposure. Prognosis is poor and only highly selected... (Review)
Review
Malignant pleural mesothelioma is a rare and aggressive malignancy mostly associated with occupational asbestos exposure. Prognosis is poor and only highly selected patients may benefit from aggressive surgical management, also as part of a multimodal approach. In advanced disease, the combination of pemetrexed and platinum remains the only established treatment, while efficacy evidence of second line chemotherapy is lacking. Thus, a deeper knowledge of biology of the disease and more effective treatments are urgently needed. Refer to specialised centres with multidisciplinary expertise is mandatory, as well as inclusion of patients in clinical trials is advisable whenever possible. In all stages of disease focus on symptoms control is paramount.
Topics: Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms
PubMed: 32156681
DOI: 10.1136/esmoopen-2019-000669 -
Cancer Genomics & Proteomics 2023Mesotheliomas are tumors similar to, and probably derived from, mesothelial cells. They carry acquired chromosomal rearrangements, deletions affecting CDKN2A,...
BACKGROUND/AIM
Mesotheliomas are tumors similar to, and probably derived from, mesothelial cells. They carry acquired chromosomal rearrangements, deletions affecting CDKN2A, pathogenetic polymorphisms in NF2, and fusion genes which often contain the promiscuous EWSR1, FUS, and ALK as partner genes. Here, we report the cytogenomic results on two peritoneal mesotheliomas.
MATERIALS AND METHODS
Both tumors were examined using G-banding with karyotyping and array comparative genomic hybridization (aCGH). One of them was further investigated with RNA sequencing, reverse transcription polymerase chain reaction (RT-PCR), Sanger sequencing, and fluorescence in situ hybridization (FISH).
RESULTS
In the first mesothelioma, the karyotype was 25∼26,X,+5,+7,+20[cp4]/50∼52,idemx2[cp7]/46,XX[2]. aCGH detected gains of chromosomes 5, 7, and 20 with retained heterozygosity on these chromosomes. In the second tumor, the karyotype was 46,XX,inv(10)(p11q25)[7]/46,XX[3]. aCGH did not detect any gains or losses and showed heterozygosity for all chromosomes. RNA sequencing, RT-PCR/Sanger sequencing, and FISH showed that the inv(10) fused MAP3K8 from 10p11 with ABLIM1 from 10q25. The MAP3K8::ABLIM1 chimera lacked exon 9 of MAP3K8.
CONCLUSION
Our data, together with information on previously described mesotheliomas, illustrate two pathogenetic mechanisms in peritoneal mesothelioma: One pathway is characterized by hyperhaploidy, but with retained disomies for chromosomes 5, 7, and 20; this may be particularly prevalent in biphasic mesotheliomas. The second pathway is characterized by rearrangements of MAP3K8 from which exon 9 of MAP3K8 is lost. The absence of exon 9 from oncogenetically rearranged MAP3K8 is a common theme in thyroid carcinoma, lung cancer, and spitzoid as well as other melanoma subtypes.
Topics: Humans; In Situ Hybridization, Fluorescence; Comparative Genomic Hybridization; Mesothelioma, Malignant; Mesothelioma; Carcinogenesis; Cell Transformation, Neoplastic; Peritoneal Neoplasms; Microfilament Proteins; LIM Domain Proteins
PubMed: 37400148
DOI: 10.21873/cgp.20388