双侧乳腺小叶原位癌中的胚系 CDH1 突变。
Germline CDH1 mutations in bilateral lobular carcinoma in situ.
机构信息
1] Research Oncology, Kings College London, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK [2] Medical and Molecular Genetics, Kings College London, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
Research Oncology, Kings College London, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
出版信息
Br J Cancer. 2014 Feb 18;110(4):1053-7. doi: 10.1038/bjc.2013.792. Epub 2013 Dec 24.
BACKGROUND
Invasive lobular breast cancer (ILC) and lobular carcinoma in situ (LCIS) are characterised by loss of E-cadherin expression. However germline CDH1 mutations are rare in cases of ILC with no family history of hereditary diffuse gastric cancer (HDGC) and have not been described in women with LCIS.
METHODS
We screened the CDH1 gene in 50 cases of bilateral LCIS/ILC using Sanger sequencing and MLPA.
RESULTS
Sanger sequencing revealed four pathogenic germline mutations, including a novel splicing mutation (c.48+1G>A). The remaining three (c.1465insC, c.1942G>T, c.2398delC) have been previously described. All four cases had bilateral LCIS +/- ILC and no family history of gastric cancer.
CONCLUSION
CDH1 germline mutations have not been previously described in women with LCIS. We have shown that germline CDH1 mutations are associated with early onset of bilateral LCIS with or without ILC in women without a family history of gastric cancer. CDH1 mutation screening should be considered in women with early onset of bilateral LCIS/ILC with no family history of HDGC.
背景
浸润性小叶乳腺癌（ILC）和小叶原位癌（LCIS）的特征是 E-钙黏蛋白表达缺失。然而，家族性弥漫性胃癌（HDGC）病史阴性的 ILC 病例中种系 CDH1 突变罕见，并且在 LCIS 女性中尚未描述。
方法
我们使用 Sanger 测序和 MLPA 对 50 例双侧 LCIS/ILC 病例的 CDH1 基因进行了筛选。
结果
Sanger 测序显示了四个致病性种系突变，包括一个新的剪接突变（c.48+1G>A）。其余三个（c.1465insC、c.1942G>T、c.2398delC）以前已经描述过。这四个病例均有双侧 LCIS +/- ILC，且无胃癌家族史。
结论
以前未在 LCIS 女性中描述过 CDH1 种系突变。我们已经表明，种系 CDH1 突变与无胃癌家族史的女性双侧 LCIS 伴或不伴 ILC 的早发有关。对于无 HDGC 家族史的双侧 LCIS/ILC 早发的女性，应考虑进行 CDH1 突变筛查。
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