Frequency and Clinical Phenotype of BAP1 Hereditary Predisposition Syndrome

Обзор

This research will have a significant impact on the overall management of those cancer patients and their family members who are at risk for hereditary cancer due to germline inactivation of BAP1. Our study will ultimately facilitate the development of novel screening, prevention and treatment strategies for these individuals with the syndrome. Because the vast majority of UM develop in pre-existing nevi, characterization of individuals at high risk for development of UM will allow closer screening and earlier intervention which would improve the treatment outcome not only for retaining vision but also for overall survival. Similarly in patients with germline BAP1 mutation CM develops in premalignant atypical melanocytic lesions and careful follow up of these patients will improve the outcome of their disease. In addition this study could have impact on the management of patients with personal and/or family history of several other cancers reported in patients with germline BAP1 mutation such as mesothelioma, renal cell carcinoma, cholangiocarcinoma, hepatocellular carcinoma, meningioma and basal cell carcinoma.

Подробное описание

BAP1 (BRCA1-associated protein-1), is a deubiquitinating enzyme with a ubiquitin carboxy-terminal hydrolase function that has been suggested to be a tumor suppressor gene with a role in cell proliferation and growth inhibition. Recently germline mutations in BAP1 have been identified by our group and others in families with hereditary cancers. However, the clinical spectrum of cancers in patients with germline BAP1 is still not clear. The association of germline BAP1 mutations with increased risks for uveal melanoma (UM), mesothelioma, cutaneous melanoma (CM), renal cell carcinoma (RCC) and BAP1-inactivated melanocytic tumors is fairly well established. However, several other cancers have been reported in these patients and their family members including cholangiocarcinoma, hepatocellular carcinoma, meningioma, basal cell carcinoma and other internal malignancies. Identification of the clinical phenotype of BAP1-TPDS is important for proper counseling and management of patients.

Первичные конечные точки

• Prevalence of germline BAP1 variants in the unselected general population of cancer patients [Срок оценки: 5 years]
• Clinical phenotypes (this includes premalignant lesions, tumor type and age of onset) in at risk blood-line family members of the patients [Срок оценки: 5 years]

Вторичные конечные точки (5)

• Questionnaire to assess environmental risk factors modifying cancer risk in patients [Срок оценки: 10 years]
• Genotyping to assess genetic risk factors modifying risk of cancer [Срок оценки: 10 years]
• Disease outcome (response to treatment, prognosis including prognostic markers) [Срок оценки: 10 years]
• Tumor pathology and genomics (including tumor grade, stage, somatic genomic alterations) [Срок оценки: 10 years]
• Assessment of disease penetrance and life time risk estimate [Срок оценки: 10 years]

Критерии участия

Критерии включения

Patients who meet any of the following criteria:

• Personal history of one cancer reported in BAP1 cancer predisposition syndrome and family history of at least two 1st or 2nd degree relatives with cancer reported in hereditary BAP1 cancer predisposition syndrome such as UM, CM, mesothelioma, RCC, cholangiocarcinoma, meningioma and hepatocellular carcinoma.
• Any patient with personal history of at least 2 cancers reported in hereditary BAP1 cancer predisposition syndrome.
• Any subject (affected or unaffected) with a documented BAP1 pathogenic/ likely pathogenic variant.
• Any patient with a cancer reported in BAP1 and a germline variant of uncertain significance.
• At risk relatives of a patient with documented BAP1 mutation.

Критерии исключения

• Study material including consent forms are currently only available in English so non-English speaking subjects are excluding

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Семейное

Центры проведения

США · 1 центр

• The Ohio State University Wexner Medical Center — Columbus

Публикации

• Godwin K, McElroy J, Senter L, Byrne L, Abdel-Rahman MH. Patient-derived outcome assessment of knowledge, communication, and management in those diagnosed with BAP1-tumor predisposition syndrome. Fam Cancer. 2026 Mar 17;25(2):28. doi: 10.1007/s10689-026-00541-8. PMID 41843333

Идентификаторы

NCT: NCT04792463 · 2014C0072

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗