Identification of New Candidate Genes for Hereditary Predisposition to Uveal Melanoma
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Identify new candidate genes for hereditary cancer predisposition in patients with uveal melanoma by constitutional exome analysis
研究概览
简要总结
Only 20% of familial uveal melanomas are explained by a hereditary predisposition, implying the presence of as yet unknown hereditary predispositions. This hypothesis is reinforced by epidemiological studies revealing an excess risk of prostate cancer, thyroid cancer and leukemia in patients who have developed uveal melanoma, even though these cancers are not part of the tumor spectrum of known hereditary predispositions to uveal melanoma (BAP1, MBD4). The identification of new candidate genes, once validated, would enable us to offer these families appropriate surveillance.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with a personal history of uveal melanoma (newly diagnosed, under treatment or in follow-up)
- •Enrolled in or benefiting from a social security scheme
排除标准
- •Causal pathogenic variation identified in BAP1 or MBD4
- •Patient does not consent to constitutional genetic analysis for diagnostic purposes
- •Patient not consenting to a constitutional genetic analysis for research purposes
- •Pregnant and breast-feeding women
- •Patients under guardianship or trusteeship
结局指标
主要结局
Identify new candidate genes for hereditary cancer predisposition in patients with uveal melanoma by constitutional exome analysis
时间窗: At baseline
Variants of interest are selected from the data using the following filter: * Variant with frequency \< 1% (GnomAD) * Shared by at least 2 sufferers in the cohort * Truncating (nonsense, with frame shift, on a canonical splice site -2, -1 and +1 +2) * Missense from a list of "cancer" genes and Combined Annotation Dependent Depletion (CADD) score \> 20 (COSMIC Tier1 and Tier2) Variants will be interpreted using various databases and prediction tools: * Functions: genecards, pubmed, uniprot * Expression profiles: cbioportal, GEPIA * For splice variants: CADD, Splice AI * For exonic variants: CADD, SIFT, Polyphene
次要结局
- Explore genes known to be involved in other cancer predisposition already described in the occurrence of uveal melanoma, but whose association has not yet been established with certainty.(At baseline)