Germline mutations in DNA repair genes predispose asbestos-exposed patients to malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer caused by asbestos exposure. An inherited predisposition has been suggested to explain multiple cases in the same family and the observation that not all individuals highly exposed to asbestos develop the tumor. Germline mutations in BAP1 are responsible for a rare cancer predisposition syndrome that includes predisposition to mesothelioma. We hypothesized that other genes involved in hereditary cancer syndromes could be responsible for the inherited mesothelioma predisposition. We investigated the prevalence of germline variants in 94 cancer-predisposing genes in 93 MPM patients with a quantified asbestos exposure. Ten pathogenic truncating variants (PTVs) were identified in PALB2, BRCA1, FANCI, ATM, SLX4, BRCA2, FANCC, FANCF, PMS1 and XPC. All these genes are involved in DNA repair pathways, mostly in homologous recombination repair. Patients carrying PTVs represented 9.7% of the panel and showed lower asbestos exposure than did all the other patients (p=0.0015). This suggests that they did not efficiently repair the DNA damage induced by asbestos and leading to carcinogenesis. This study shows that germline variants in several genes may increase MPM susceptibility in the presence of asbestos exposure and may be important for specific treatment

Orbital Meningoencephalocele Due to Extraventricular Neurocytoma: Case Report

Extraventricular Neurocytoma (EVN) is a rare primary tumor of Central Nervous System (CNS). To date, no cases have been reported in International Literature, about EVN associated to meningoencephalocele as manifestation of subacute increased intracranial pressure.We report the first case of EVN that manifested with diplopia and ocular motor disorders due to intraorbital meningoencephalocele through a bone gap in the orbital roof.Diagnosis of EVN is challenging and its differential diagnosis with more aggressive lesions is mandatory. Complete surgical removal does not need any adiuvant therapies and permits to control tumor growth and symptoms related to intracranial pressure.</p

Use of the Heterocypris incongruens bioassay for assessing ecotoxicity of soils containing the anionic surfactant sodium lauryl ether sulphate (SLES)

The production and consumption of surfactants are constantly increasing, and huge amounts are found in the environment as contaminants. Surfactants are widely used in domestic and industrial applications, including in tunnel-mechanized excavation of large-scale infrastructures (e.g. highways and railways). In the latter case, the commercial products are foaming agents containing the anionic surfactant sodium lauryl ether sulphate (SLES). Foaming agents are necessary for enhancing Tunnel Boring Machine-Earth Pressure Balance (TBM-EPB) performance. Consequently, there are SLES concentrations in excavated soils of which large quantities can have harmful effects on biota. SLES toxicity in the aquatic environment is well known; on the contrary, knowledge of its effects on soil organisms is quite limited. In order to better understand SLES ecotoxicity in soil, the standardized bioassay (ISO 14371:2012) with the crustacean Heterocypris incongruens, living in the soil–water interface, was used. The lethal concentrations of standard SLES (LC15: 120; LC50: 140 mg/L, respectively) and of three common commercial products used as foaming agents (LC50 varying from 275 to 3810 mg/L) were evaluated. Subsequently, the crustacean acute and sub-chronic effects (mortality and growth inhibition) were assessed in seven different excavated soils conditioned with various commercial products. In addition, SLES concentrations in each soil and in their soil water extract were also determined. Mortality was not recorded in soils conditioned with foaming agents; however, a growth inhibition (c.a. 61.6 %) was found for soils with a high fine fraction and conditioned with high amounts (≥2 L/m3 soil) of foaming agents. H. incongruens proved to be an appropriate bioassay for assessing the possible effects of high SLES concentrations in soil, especially when this surfactant is bound to soil

Differential Diagnosis of Malignant Pleural Mesothelioma on Cytology: A Gene Expression Panel Versus BRCA1-Associated Protein 1 and p16 Tests

Pleural effusions are among the first clinical manifestations of malignant pleural mesothelioma (MPM) and often constitute the only available material for diagnosis. Although an MPM diagnosis can be reliable on cytology, the reported sensitivity is low (30% to 75%). Particularly, it can be hard to discriminate epithelioid MPM, the most common histotype, from reactive mesothelial hyperplasia (MH). Currently, BRCA1-associated protein 1 (BAP1) and CDKN2A (p16), evaluated by immunohistochemistry and fluorescent in situ hybridization, respectively, are the most valuable markers to discriminate MPM and MH. Both markers have a high specificity, but their sensitivity is not always satisfying, even when used together. We have recently developed a 117-gene expression panel, based on Nanostring technology, able to differentiate epithelioid MPM from MH pleural tissues better than BAP1 and p16. Herein, we evaluated the efficacy of the same panel on an independent retrospective cohort of 23 MPM and 11 MH pleural effusions (cell blocks and smears). The overall sensitivity and specificity of the panel were equal to 0.9565 and 1, respectively. Moreover, the panel performance was compared with BAP1 and p16 on 25 cell blocks. Sensitivity levels of gene panel, BAP1 alone, p16 alone, and BAP1 plus p16 were 1, 0.5882, 0.4706, and 0.7647, respectively. Specificity was always 1. Although further validation is needed, this gene panel could really facilitate patients' management, allowing a definitive MPM diagnosis directly on pleural effusions

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types