来自印度南部喀拉拉邦的96个遗传性乳腺癌和乳腺-卵巢癌家族中BRCA2基因的新型种系突变。

Novel germline mutations in BRCA2 gene among 96 hereditary breast and breast-ovarian cancer families from Kerala, South India.

作者信息

Syamala Vani, Sreeja Leelakumari, Syamala Volga S, Vinodkumar B, Raveendran Praveenkumar B, Sreedharan Hariharan, Kuttappan Ratheesan, Balakrishnan Lekshmi, Ankathil Ravindran

机构信息

Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, Kerala, 695011, India.

出版信息

J Cancer Res Clin Oncol. 2007 Nov;133(11):867-74. doi: 10.1007/s00432-007-0229-6. Epub 2007 May 15.

DOI:10.1007/s00432-007-0229-6

PMID:17503080

Abstract

PURPOSE

Aim of the present study was to identify the genetic heterogeneity, prevalence and frequency of germline mutations of BRCA2 gene in Hereditary Breast/Ovarian cancer patients from Kerala, South India.

METHODS

We analyzed 102 Breast/Ovarian cancer patients from 96 breast and/ovarian cancer families for BRCA2 gene mutations using Conformation-Sensitive Gel Electrophoresis (CSGE) followed by sequencing.

RESULTS

Sequence variations in BRCA2 gene were detected in 27 (26.4%) patients. Sixteen distinct sequence variants were detected of which 11 were (69%) in exon 11. We have identified two novel disease-causing frameshift mutations (c.4642delAA and c.4926insGACC) in two unrelated patients. Apart from this, fourteen distinct sequence variants were detected in 25 breast/ovarian cancer patients of which 8 (57%) were also novel. These include nine missense mutations, one silent mutation, one-nonsense mutation and three intronic variants.

CONCLUSIONS

The results of this study suggest that germline mutations of BRCA2 gene account for rather small proportion of Hereditary Breast/Ovarian cancer in Kerala, South India.

摘要

目的

本研究旨在确定印度南部喀拉拉邦遗传性乳腺癌/卵巢癌患者中BRCA2基因的遗传异质性、种系突变的患病率和频率。

方法

我们使用构象敏感凝胶电泳（CSGE）随后进行测序，分析了来自96个乳腺癌和/或卵巢癌家族的102例乳腺癌/卵巢癌患者的BRCA2基因突变情况。

结果

在27例（26.4%）患者中检测到BRCA2基因的序列变异。检测到16种不同的序列变异，其中11种（69%）在外显子11中。我们在两名无亲缘关系的患者中鉴定出两种新的致病移码突变（c.4642delAA和c.4926insGACC）。除此之外，在25例乳腺癌/卵巢癌患者中检测到14种不同的序列变异，其中8种（57%）也是新的。这些包括9种错义突变、1种沉默突变、1种无义突变和3种内含子变异。