11q13 内的 7Mb 区域可能包含乳腺癌的高外显率基因。

A 7 Mb region within 11q13 may contain a high penetrance gene for breast cancer.

机构信息

Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernandez Almagro 3, Madrid, 28029, Spain.

出版信息

Breast Cancer Res Treat. 2009 Nov;118(1):151-9. doi: 10.1007/s10549-009-0317-1. Epub 2009 Feb 10.

DOI:10.1007/s10549-009-0317-1

PMID:19205878

Abstract

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.

摘要

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。