A population study of mutations and LOH at breast cancer gene loci in tumours from sister pairs: two recurrent mutations seem to account for all BRCA1/BRCA2 linked breast cancer in Iceland
A population study of mutations and LOH at breast cancer gene loci in tumours from sister pairs: two recurrent mutations seem to account for all BRCA1/BRCA2 linked breast cancer in Iceland
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DOI：
10.1136/jmg.35.6.446
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发表时间：
1998-06-01
影响因子：
4
通讯作者：
Egilsson, V
中科院分区：
文献类型：
--
作者：
Arason, A;Jonasdottir, A;Egilsson, V
高危家族中的大多数乳腺癌被认为是由两个名为BRCA1和BRCA2的基因中的一个突变造成的。任何一种基因的生殖系缺陷通常伴随着肿瘤中正常等位基因的染色体缺失。在冰岛已经发现了两个反复发生的突变，999de15 BRCA2和G5193A BRCA1。在这项研究中，随机选择一对60岁或更年轻的姐妹被诊断为乳腺癌，以评估导致BRCA1和BRCA2前部乳腺癌的比例。使用BRCA1内部和周围的标记，比较了42对姐妹肿瘤组织中的基因类型和等位基因丢失。和BRCA2基因。11对姊妹对高度提示BRCA2连锁，未发现明显的BRCA1连锁。对G5193A BRCA1和999de15 BRCA2突变的筛查显示，在II BRCA2提示对中999de15突变加上3对不代表连锁的突变，在1对中发现G5193A BRCA1突变。当已知的突变携带者从该组中移除时，没有迹象表明进一步与BRCA1或BRCA2连锁。我们的研究结果表明，冰岛很大一部分家族性乳腺癌是999de15 BRCA2突变的结果，除了999de15和G5193A外，BRCA1和BRCA2胚系突变不太可能在冰岛遗传性乳腺癌中发挥重要作用。此外，通过研究BRCA1或BRCA2连锁缺失基因周围的杂合性缺失，可以很容易地识别出大多数BRCA1或BRCA2连锁的家系。
The majority of breast cancer in high risk families is believed to result from a mutation in either of two genes named BRCA1 and BRCA2. A germline defect in either gene is usually followed by chromosomal deletion of the normal allele in the tumour. In Iceland two recurrent mutations have been identified, 999de15 BRCA2 and G5193A BRCA1. In this study, randomly selected pairs of sisters diagnosed with breast cancer at the age of 60 years or younger were analysed to evaluate the proportion of breast cancer resulting front BRCA1 and BRCA2. Genotypes and allele loss in tumour tissue from 42 sister pairs were compared using markers within and around the BRCA1. and BRCA2 genes. Eleven sister pairs were highly suggestive of BRCA2 linkage, and no obvious BRCA1 linkage was seen. Screening for the G5193A BRCA1 and 999de15 BRCA2 mutations showed the 999de15 mutation in the II BRCA2 suggestive pairs plus three pairs less indicative of linkage, and the G5193A BRCA1 mutation in one pair. When known mutation carriers are removed from the group, no indication of further linkage to BRCA1 or BRCA2 is seen. The results of our studies suggest that a large proportion of familial breast cancer in Iceland is the result of the 999de15 BRCA2 mutation, and it is unlikely that BRCA1 and BRCA2 germline mutations other than 999de15 and G5193A play a significant role in hereditary breast cancer in Iceland. Furthermore it can be concluded that most families with BRCA1 or BRCA2 linkage are easily identified by studying LOH around the defective gene in as feu as two affected relatives.