Focal malformations of cortical development (FMCDs), including focal cortical dysplasia (FCD) and hemimegalencephaly (HME), are major etiologies of pediatric intractable epilepsies exhibiting cortical dyslamination. Brain somatic mutations in MTOR have recently been identified as a major genetic cause of FMCDs. However, the molecular mechanism by which these mutations lead to cortical dyslamination remains poorly understood. Here, using patient tissue, genome-edited cells, and mouse models with brain somatic mutations in MTOR, we discovered that disruption of neuronal ciliogenesis by the mutations underlies cortical dyslamination in FMCDs. We found that abnormal accumulation of OFD1 at centriolar satellites due to perturbed autophagy was responsible for the defective neuronal ciliogenesis. Additionally, we found that disrupted neuronal ciliogenesis accounted for cortical dyslamination in FMCDs by compromising Wnt signals essential for neuronal polarization. Altogether, this study describes a molecular mechanism by which brain somatic mutations in MTOR contribute to the pathogenesis of cortical dyslamination in FMCDs.

With the prevalence of malignant melanoma increasing gradually and the progressive westernization of the Asian lifestyle, it is important to analyze and follow up on the characteristics of malignant melanoma at regular intervals. We identified the characteristics of malignant melanoma by analyzing consecutive patients from a single medical center. We also examined the trend of malignant melanoma and prognostic factors in Asian patients. We investigated 200 consecutive patients with malignant melanoma in a single medical center between 2000 and 2022. Each patient’s sex and age, tumor stage, site of the primary lesion, histological subtype, Breslow thickness, Clark level, and period of survival were collected from the historical medical records of the patients and analyzed. Survival analyses were performed using the Kaplan–Meier method to investigate the prognostic factors. The ratio of man-to-woman was 1:1.53; the most common site of the primary tumor was the lower extremity (60%), and acral lentiginous melanoma was the most common histological subtype (61%). Malignant melanoma commonly occurs in the lower extremities, primarily in the form of the lentiginous subtype. In situ melanomas are most prevalent regarding Breslow thickness, while Clark Level 4 is the most common type of malignant melanoma. Sex and Breslow thickness were significantly associated with the survival rate. However, others were not significant prognostic indicators for survival in this cohort. This study confirmed that the epidemiology of malignant melanoma in Asian patients was maintained without significant change. We also confirmed several significant prognostic indicators for survival.