在有遗传性扩散性胃癌的家庭中,创始和复发的CDH1突变
Pardeep Kaurah1, Andrée MacMillan, Niki Boyd
1Hereditary Cancer Program, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
JAMA
|June 5, 2007
概括
在遗传性扩散性胃癌家族中,经常出现的CDH1突变来自新的事件和共同的祖先. 强烈表明来自纽芬兰的创始人突变,影响胃癌和乳腺癌风险.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 癌症生物学 癌症生物学
- 流行病学 流行病学
背景情况:
- 遗传性扩散性胃癌 (HDGC) 与上皮卡德林 (CDH1) 基因的生殖基因突变有关.
- HDGC显著增加了扩散性胃癌和叶状乳腺癌的风险.
研究的目的:
- 调查复发的生殖系CDH1突变是否来自独立的突变事件或共同的祖先.
- 为了确定CDH1突变在HDGC家族的起源.
主要方法:
- 对38个患有遗传性扩散性胃癌的家庭进行了对CDH1突变的分析.
- 对14个家族 (7个来自本研究,7个先前报告) 进行了哈普类型分析,以评估复发突变的共同祖先.
主要成果:
- 在15个家族中发现了13种CDH1突变,包括6种新型突变 (40%的检测率).
- 特定突变 (1137G>A,1901C>T,2064-2065delTG) 显示出共同和独立起源的证据.
- 在四个来自纽芬兰的家庭中发现了一个创始基因突变 (2398delC),在75岁时具有显著的胃癌 (男性40%,女性63%) 和乳腺癌 (女性52%) 的累积风险.
结论:
- 在HDGC家族中反复发生的CDH1突变归因于独立事件和共同祖先.
- 强有力的证据支持来自纽芬兰的创始突变,影响受影响家庭的癌症风险.
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