Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernandez Almagro 3, Madrid, 28029, Spain.
Breast Cancer Res Treat. 2009 Nov;118(1):151-9. doi: 10.1007/s10549-009-0317-1. Epub 2009 Feb 10.
Familial breast cancer represents up to 5% of all breast cancer cases. Recently, our group has performed a new SNP-based linkage study in 19 non-BRCA1/2 families. We found that a single family was linked to regions in two different chromosomes (11q13 and 14q21), and observed a non-parametric LOD score of 11.5 in both regions. In the present study, we ruled out any possible translocation between the chromosomes. We also used both a panel of STRs and an indirect approach based on HapMap data to narrow down these regions from 28 to 7 Mb in chromosome 11 and from 14.5 to 8.5 Mb in chromosome 14. We performed a mutational screening on candidate genes in 11q13 (NUMA1, FGF3, CCND1, RAD9A, RNF121, FADD and hsa-mir-192), and on FOXA1 in 14q21. Although we have not found any deleterious mutations in the coding region of these genes, data from STR markers confirm 11q13 as a candidate region to contain a breast cancer susceptibility gene.
家族性乳腺癌占所有乳腺癌病例的 5%。最近，我们小组对 19 个非 BRCA1/2 家族进行了一项新的基于 SNP 的连锁研究。我们发现一个家族与两个不同染色体（11q13 和 14q21）的区域连锁，并在两个区域观察到非参数 LOD 评分 11.5。在本研究中，我们排除了染色体之间任何可能的易位。我们还使用了 STR 面板和基于 HapMap 数据的间接方法，将这两个区域从 11 号染色体上的 28Mb 缩小到 7Mb，从 14 号染色体上的 14.5Mb 缩小到 8.5Mb。我们对 11q13 中的候选基因（NUMA1、FGF3、CCND1、RAD9A、RNF121、FADD 和 hsa-mir-192）和 14q21 中的 FOXA1 进行了突变筛选。尽管我们在这些基因的编码区没有发现任何有害突变，但 STR 标记的数据证实 11q13 是一个包含乳腺癌易感基因的候选区域。
