Mesothelioma

2023-05-06 Yin (Rex) Hung, MD Affiliation

1.Massachusetts General Hospital and Harvard Medical School, Boston

Classification

Definition

Mesotheliomas are tumors of mesothelial differentiation that arise from the serosal membrane(s), most commonly the pleura, less commonly pericardium, peritoneum, or tunica vaginalis ^1,2.

Mesothelioma	Genetic marker(s)
Localized pleura mesothelioma	Localized mesothelioma appears genetically heterogeneous with multiple subgroups: (1) BAP1 mutations with deletions of CDKN2A and NF2; (2) TRAF7 mutations, including one case described with trisomies of chromosomes 3, 5, 7, and X; and (3) genomic near-haploidization with extensive loss of heterozygosity however sparing chromosomes 5 and 7.^3,4
Diffuse pleural mesothelioma	Somatic mutations involving tumor suppressors/epigenetic regulators BAP1, SETD2, NF2, DDX3X, PBRM1, and others are typical and have been detected in a substantial fraction of tumors, including those originating in the pleura or the peritoneum.^5-9 Other somatic alterations including loss of CDKN2A and mutations involving TP53 can be seen in some tumors. While most of these mutations are typically somatic, germline mutations involving BAP1 or other genes can be present in a subset of patients.^10,11 Rarely, oncogenic gene rearrangements involving ALK can be identified, particularly in children or young adults.^12-15 Other rare alterations include those with EWSR1::ATF1 fusion ^16,17 and those with genomic near-haploidization.^8,9,18
Sarcomatoid mesothelioma	Less likely harbor BAP1 mutations and more likely to harbor TP53 and/or CDKN2A alterations as compared to epithelioid mesothelioma.^6,8,19
Epithelioid mesothelioma	see above in diffuse pleural mesothelioma
Biphasic mesothelioma	see above in diffuse pleural mesothelioma

Article Bibliography

Reference Number	Pubmed ID	Last Year	Title	Authors
1	29708148	2018	Novel insights and recent discoveries on the genetics and pathogenesis of malignant mesothelioma.	Hung YP et al
2	33012427	2020	Pathology of Malignant Pleural Mesothelioma.	Hung YP et al
3	31371807	2020	Molecular characterization of localized pleural mesothelioma.	Hung YP et al
4	31485011	2020	Localized malignant mesothelioma, an unusual and poorly characterized neoplasm of serosal origin: best current evidence from the literature and the International Mesothelioma Panel.	Marchevsky AM et al
5	21642991	2011	The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma.	Bott M et al
6	26928227	2016	Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations.	Bueno R et al
7	27813512	2017	Genomic profiling of malignant peritoneal mesothelioma reveals recurrent alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X.	Joseph NM et al
8	30322867	2018	Integrative Molecular Characterization of Malignant Pleural Mesothelioma.	Hmeljak J et al
9	32504035	2020	Molecular characterization of diffuse malignant peritoneal mesothelioma.	Hung YP et al
10	21874000	2011	Germline BAP1 mutations predispose to malignant mesothelioma.	Testa JR et al
11	30113886	2018	Frequency of Germline Mutations in Cancer Susceptibility Genes in Malignant Mesothelioma.	Panou V et al
12	26179668	2016	Anaplastic lymphoma kinase (ALK) translocation in paediatric malignant peritoneal mesothelioma: a case report of novel ALK-related tumour spectrum.	Loharamtaweethong K et al
13	28910456	2018	Identification of ALK Rearrangements in Malignant Peritoneal Mesothelioma.	Hung YP et al
14	31783178	2020	Anaplastic Lymphoma Kinase Gene Rearrangement in Children and Young Adults With Mesothelioma.	Mian I et al
15	33399341	2021	Pediatric Mesothelioma With ALK Fusions: A Molecular and Pathologic Study of 5 Cases.	Argani P et al
16	28505004	2017	A Subset of Malignant Mesotheliomas in Young Adults Are Associated With Recurrent EWSR1/FUS-ATF1 Fusions.	Desmeules P et al
17	34121509	2021	Malignant Mesothelioma With EWSR1-ATF1 Fusion in Two Adolescent Male Patients.	Ren H et al
18	34648949	2022	Molecular Characterization of Peritoneal Mesotheliomas.	Offin M et al
19	32944962	2021	Large-scale analysis of BAP1 expression reveals novel associations with clinical and molecular features of malignant pleural mesothelioma.	De Rienzo A et al

External Links

Citation

Yin (Rex) Hung, MD

Mesothelioma

Atlas Genet Cytogenet Oncol Haematol. 2023-05-06