RESUMEN
The BAP1 gene (BRCA1-associated protein 1) is a tumour suppressor gene that encodes a deubiquitinating enzyme (DUB), regulating key cellular pathways, including cell cycle, cellular differentiation, transcription and DNA damage response. Germline BAP1 mutations cause a novel cancer syndrome characterised by early onset of multiple atypical Spitz tumours and increased risk of uveal and cutaneous melanoma, mesothelioma, renal cell carcinoma and various other malignancies. Recognising the clinicopathological features of specific BAP1-deficient tumours is crucial for early screening/tumour detection, with significant impact on patient outcome.
Asunto(s)
Mutación de Línea Germinal , Melanoma/genética , Mesotelioma/genética , Nevo de Células Epitelioides y Fusiformes/genética , Neoplasias Cutáneas/genética , Proteínas Supresoras de Tumor/genética , Ubiquitina Tiolesterasa/genética , Humanos , Melanoma/metabolismo , Melanoma/patología , Mesotelioma/metabolismo , Mesotelioma/patología , Nevo de Células Epitelioides y Fusiformes/metabolismo , Nevo de Células Epitelioides y Fusiformes/patología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina Tiolesterasa/metabolismo , Melanoma Cutáneo MalignoRESUMEN
OBJECTIVE: Systemic lupus erythematosus (SLE) is typically a relapsing/remitting disease. However, some patients experience prolonged remission. These patients may provide further insights into SLE pathophysiology. In this study we characterize their clinical course. METHODS: Prolonged remission was defined as Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) = 0, = 2, or = 4 (based on serology) for ≥ 5 consecutive years, with visits ≤ 18 months apart. The patients could be taking antimalarials, but not corticosteroids or immunosuppressives. Flare was defined as clinical activity on SLEDAI-2K, or by corticosteroid/immunosuppressive initiation. Each patient's preremission course was classified as monophasic, relapsing/remitting, or chronic active. These patients were compared to matched SLE controls and patients achieving remission on medications. RESULTS: A total of 38/1613 (2.4%) patients achieved prolonged remission while taking no medications. The mean duration was 11.5 ± 6.4 years. Twenty-seven patients (71.0%) had relapsing/remitting disease, 11 (28.9%) had monophasic illness, and none had chronic active disease prior to remission. They differed from matched controls in ethnicity, disease activity at first visit, and cumulative organ damage. There were 34/1613 patients (2.1%) who achieved prolonged remission while taking steroids and/or immunosuppressives, with mean duration 8.5 ± 2.9 years. Twelve patients (35.3%) experienced disease flare. They were younger at diagnosis, with more disease activity prior to remission than patients taking no medications. CONCLUSION: Prolonged remission is an infrequent outcome among patients and is preceded by an atypically monophasic clinical course in a significant minority. Those taking medications represent a heterogeneous group: those who will tolerate eventual taper, and those whose disease activity was merely suppressed by ongoing immunosuppression. Prolonged remission may reflect unique pathophysiologic mechanisms, and warrants further investigation.