Real-Life Outcomes of Adjuvant Targeted Therapy and Anti-PD1 Agents in Stage III/IV Resected Melanoma.

This study was carried out at the Dermatologic Clinic of the University of Turin, Italy, to assess the effectiveness and safety of adjuvant therapy in patients who received either targeted therapy (TT: dabrafenib + trametinib) or immunotherapy (IT: nivolumab or pembrolizumab) for up to 12 months. A total of 163 patients participated, including 147 with stage III and 19 with stage IV with no evidence of disease. The primary outcomes were relapse-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS).

Dominantly acting variants in ATP6V1C1 and ATP6V1B2 cause a multisystem phenotypic spectrum by altering lysosomal and/or autophagosome function.

The vacuolar H-ATPase (V-ATPase) is a functionally conserved multimeric complex localized at the membranes of many organelles where its proton-pumping action is required for proper lumen acidification. The V-ATPase complex is composed of several subunits, some of which have been linked to human disease. We and others previously reported pathogenic dominantly acting variants in ATP6V1B2, the gene encoding the V1B2 subunit, as underlying a clinically variable phenotypic spectrum including dominant deafness-onychodystrophy (DDOD) syndrome, Zimmermann-Laband syndrome (ZLS), and deafness, onychodystrophy, osteodystrophy, intellectual disability, and seizures (DOORS) syndrome.

Germline bi-allelic alteration predisposes to a neonatal juvenile myelomonocytic leukemia-like disorder.

Juvenile myelomonocytic leukemia (JMML) is a rare, generally aggressive myeloproliferative neoplasm affecting young children. It is characterized by granulomonocytic expansion, with monocytosis infiltrating peripheral tissues. JMML is initiated by mutations upregulating RAS signaling.

Enhancer hijacking at the ARHGAP36 locus is associated with connective tissue to bone transformation.

Heterotopic ossification is a disorder caused by abnormal mineralization of soft tissues in which signaling pathways such as BMP, TGFβ and WNT are known key players in driving ectopic bone formation. Identifying novel genes and pathways related to the mineralization process are important steps for future gene therapy in bone disorders. In this study, we detect an inter-chromosomal insertional duplication in a female proband disrupting a topologically associating domain and causing an ultra-rare progressive form of heterotopic ossification.