一个POT1创始人变异与早期出现的复发性黑色素瘤和各种固体恶性瘤有关
Aasem Abu Shtaya1,2, Inbal Kedar1, Lily Bazak1
1Recanati Genetics Institute, Rabin Medical Center-Beilinson Hospital, Petach Tikva 4941492, Israel.
Genes
|March 28, 2024
概括
一种POT1基因变异,p.(I78T),是阿什基纳兹犹太人的创始病原性突变,显著增加了早期黑色素瘤和其他癌症的风险. 对于这种血统的高风险个体,推进行基因检测.
科学领域:
- 遗传学和基因组学 在
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 保护端粒1 (POT1) 对于在shelterin复合体内的端粒维护至关重要.
- 生殖系POT1变异与遗传性癌症有关,特别是黑色素瘤和慢性淋巴细胞白血病 (CLL).
- 此前,POT1 p. ((I78T) 变种的致病性一直是不确定的.
研究的目的:
- 确定POT1 p.(I78T) 作为阿什基纳兹犹太人 (AJs) 的创始病原体变体.
- 描述与这种特定的POT1变异相关的临床谱.
- 确定AJs中POT1 p.(I78T) 变种的流行率和遗传背景.
主要方法:
- 针对接受遗传咨询 (2018-2023) 的个人进行定向数据库搜索.
- 从已识别的载体收集和分析人口,临床,遗传和病理数据.
- 对Exome数据库的审查,以评估不同种族群体的变异频率,以及为确认创始人效应而进行的哈普类型分析.
主要成果:
- 来自十个家庭的11名携带者被确定,他们都是阿什基纳兹犹太裔.
- 携带者呈现出高瘤负担,在家族中平均有30种主要恶性瘤.
- 早期发生的黑色素瘤 (82%),瘤 (27%),乳腺癌 (27%),乳腺癌 (63%).
- 变异频率在AJs中为0.25%,而在一般人群中为0.06%;共享的原型证实了创始人身份.
结论:
- POT1 p.(I78T) 是阿什基纳兹犹太人的创始病原体变体,与早期发生的黑色素瘤和各种固体瘤密切相关.
- 这种变体对多种原发性癌症具有显著的风险,表明瘤负担很高.
- 对于阿什基纳兹犹太血统的高风险个体,建议对POT1进行基因检测,在癌症生殖基因组中应考虑POT1.
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