Somatic allele loss in genetic linkage analysis of cancer.
Somatic allele loss in genetic linkage analysis of cancer.
复制标题
癌症遗传连锁分析中的体细胞等位基因丢失。
DOI：
10.1002/gepi.1370110504
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发表时间：
1994
影响因子：
2.1
通讯作者：
Buetow,KH
中科院分区：
文献类型：
--
作者：
Rebbeck,TR;Lustbader,ED;Buetow,KH
在人类癌症研究中检测或拒绝遗传连锁的能力通常会降低，因为无法对谱系中多个受影响的亲属进行分析。肿瘤中体细胞等位基因丢失的观察可以提供有关配子期的知识。因此，考虑肿瘤基因型数据可用于获取通常从癌症家族的较大样本中获得的配子期知识。本研究的目的是描述一种通过利用肿瘤组织中体细胞遗传变化的知识来提高检测或拒绝遗传连锁的能力的方法。提出了对连锁分析的 lod 评分方法的修改，其中连锁可能性中配子期的知识是从肿瘤组织中组成杂合性 (LoH) 损失的观察中推断出来的。使用具有一对后代的双回交核心家族对该方法进行了评估。当分析中包含肿瘤基因型数据时，预期的 lod 评分显着提高。例如，当肿瘤组织中保留的单倍型在 99% 的情况下与构成组织中的遗传单倍型相同时，与结合肿瘤基因型数据的分析相比，没有肿瘤基因型数据的连锁分析将需要 2-5 倍大的后代对样本才能得出 3 或更高的预期 Lod 评分值的连锁。这些结果表明，使用所提出的方法考虑肿瘤基因型数据可以显着提高癌症家族连锁分析的能力。 © 1994 Wiley-Liss, Inc.
The ability to detect or reject genetic linkage in studies of human cancer is often diminished because multiple affected relatives in a pedigree are unavailable for analysis. The observation of somatic allele loss in tumors can provide knowledge about gametic phase. Therefore, consideration of tumor genotype data could be used to obtain knowledge about gametic phase ordinarily gained from a larger sample of individuals in cancer families. The objective of the present study is to describe a method for improving the power to detect or reject genetic linkage by using knowledge about somatic genetic changes in tumor tissue. A modification to the lod score method of linkage analysis is proposed in which knowledge of gametic phase in the linkage likelihood is inferred from observations of loss of constitutional heterozygosity (LoH) in tumor tissue. This methodology was evaluated using a double backcross nuclear family with a pair of offspring. The expected lod score improved substantially when tumor genotype data were included in the analysis. For example, when the haplotype remaining in tumor tissue was identical to the inherited haplotype in constitutional tissue 99% of the time, linkage analyses without tumor genotype data would require a 2–5 times larger sample of offspring pairs to conclude linkage with an expected lod score value of 3 or greater, compared to analyses incorporating tumor genotype data. These results suggest that consideration of tumor genotype data using the proposed method can substantially improve the power of linkage analyses in cancer families. © 1994 Wiley‐Liss, Inc.