Medical and Surgical Care of Patients With Mesothelioma and Their Relatives Carrying Germline BAP1 Mutations.

The most common malignancies that develop in carriers of BAP1 germline mutations include diffuse malignant mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma, and less frequently, breast cancer, several types of skin carcinomas, and other tumor types. Mesotheliomas in these patients are significantly less aggressive, and patients require a multidisciplinary approach that involves genetic counseling, medical genetics, pathology, surgical, medical, and radiation oncology expertise. Some BAP1 carriers have asymptomatic mesothelioma that can be followed by close clinical observation without apparent adverse outcomes: they may survive many years without therapy.

Systematic review and meta-analysis of genomic alterations in acral melanoma.

Acral melanoma (AM) tumors arise on the palms, soles, fingers, toes, and nailbeds. A comprehensive systematic meta-analysis of AM genomic aberrations has not been conducted to date. A literature review was carried out to identify studies sequencing AM.

Assessing Sunscreen Protection Using UV Photography: Descriptive Study.

Background: Photography using a UV transmitting filter allows UV light to pass and can be used to illuminate UV blocking lotions such as sunscreens.

Objective: The aim of this study is to compare currently available UV photography cameras and assess whether these devices can be used as visualization tools for adequate coverage of sun protection lotions.

Methods: This study was conducted in 3 parts: in phase 1, 3 different UV cameras were tested; in phase 2, we explored whether UV photography could work on a range of sun protection products; and in phase 3, a UV webcam was developed and was field-tested in a beach setting.

Meta-Analysis and Systematic Review of the Genomics of Mucosal Melanoma.

Mucosal melanoma is a rare subtype of melanoma. To date, there has been no comprehensive systematic collation and statistical analysis of the aberrations and aggregated frequency of driver events across multiple studies. Published studies using whole genome, whole exome, targeted gene panel, or individual gene sequencing were identified.

Microsimulation Model for Evaluating the Cost-Effectiveness of Surveillance in Pathogenic Variant Carriers.

Purpose: Pathogenic germline variants cause a tumor-predisposition syndrome (-TPDS) linked to uveal melanoma, mesothelioma, cutaneous melanoma, and renal cell carcinoma. Surveillance of carriers of pathogenic variants provides an opportunity for early tumor detection; however, there are no evidence-based guidelines for management of -TPDS, nor health economic evaluation; this study aims to provide this evidence.

Methods: We created a Markov microsimulation health state transition model of germline carriers to predict if active surveillance for the four main tumors influences survival and improves associated economic costs with a time horizon of 100 years from the perspective of the healthcare system (N = 10,000).

Combined use of subclinical hydroxyurea and CHK1 inhibitor effectively controls melanoma and lung cancer progression, with reduced normal tissue toxicity compared to gemcitabine.

Drugs such as gemcitabine that increase replication stress are effective chemotherapeutics in a range of cancer settings. These drugs effectively block replication and promote DNA damage, triggering a cell cycle checkpoint response through the ATR-CHK1 pathway. Inhibiting this signalling pathway sensitises cells to killing by replication stress-inducing drugs.

Comprehensive Study of the Clinical Phenotype of Germline BAP1 Variant-Carrying Families Worldwide.

Background: The BRCA1-associated protein-1 (BAP1) tumor predisposition syndrome (BAP1-TPDS) is a hereditary tumor syndrome caused by germline pathogenic variants in BAP1 encoding a tumor suppressor associated with uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and cutaneous BAP1-inactivated melanocytic tumors. However, the full spectrum of tumors associated with the syndrome is yet to be determined. Improved understanding of the BAP1-TPDS is crucial for appropriate clinical management of BAP1 germline variant carriers and their families, including genetic counseling and surveillance for new tumors.

Endogenous Replication Stress Marks Melanomas Sensitive to CHEK1 Inhibitors .

Checkpoint kinase 1 inhibitors (CHEK1i) have single-agent activity and Here, we have investigated the molecular basis of this activity. We have assessed a panel of melanoma cell lines for their sensitivity to the CHEK1i GNE-323 and GDC-0575 and The effects of these compounds on responses to DNA replication stress were analyzed in the hypersensitive cell lines. A subset of melanoma cell lines is hypersensitive to CHEK1i-induced cell death , and the drug effectively inhibits tumor growth In the hypersensitive cell lines, GNE-323 triggers cell death without cells entering mitosis.