Copy number variants associated with 18p11.32, DCC and the promoter 1B region of APC in colorectal polyposis patients
Copy number variants associated with 18p11.32, DCC and the promoter 1B region of APC in colorectal polyposis patients
复制标题
DOI：
10.1016/j.mgene.2015.12.005
复制
发表时间：
2016-02-01
期刊：
影响因子：
0.7
通讯作者：
Scott, Rodney J.
中科院分区：
文献类型：
--
作者：
Masson, Amy L.;Talseth-Palmer, Bente A.;Scott, Rodney J.
家族性腺瘤性息肉病（FAP）是第二种最常见的结直肠癌（CRC）遗传易感性，与结肠和直肠中数百至数千个腺瘤的发展相关。APC突变在类似于80%的FAP息肉病患者中发现。在剩下的20%中，不能提供遗传诊断，这表明使APC失活的其他基因或机制可能是负责的。拷贝数变异（CNVs）在FAP中仍有待研究，可能是一部分息肉病患者的病因。使用2.7M微阵列（Affyoung）筛选56名息肉病患者和40名对照的队列的CNV，使用ChAS（Affyoung）分析数据。共鉴定出142个息肉病队列特有的CNV，表明它们参与CRC风险。我们在4名不相关的息肉病患者中明确鉴定了CRC易感基因APC、DCC、MLH1和CTNNB1中的CNV，这些基因可能有助于这些患者的疾病发展。在9%的患者中观察到18p11.32位置的复发性缺失，这是特别感兴趣的。考虑到筛查患者的高患病率，有必要进行进一步调查，以充分了解这些变异在CRC风险中的作用。皇冠版权所有（C）2016由Elsevier B.V.
Familial Adenomatous Polyposis (FAP) is the second most common inherited predisposition to colorectal cancer (CRC) associated with the development of hundreds to thousands of adenomas in the colon and rectum. Mutations in APC are found in similar to 80% polyposis patients with FAP. In the remaining 20% no genetic diagnosis can be provided suggesting other genes ormechanisms that render APC inactive may be responsible. Copy number variants (CNVs) remain to be investigated in FAP and may account for disease in a proportion of polyposis patients. A cohort of 56 polyposis patients and 40 controls were screened for CNVs using the 2.7M microarray (Affymetrix) with data analysed using ChAS (Affymetrix). A total of 142 CNVs were identified unique to the polyposis cohort suggesting their involvement in CRC risk. We specifically identified CNVs in four unrelated polyposis patients among CRC susceptibility genes APC, DCC, MLH1 and CTNNB1 which are likely to have contributed to disease development in these patients. A recurrent deletion was observed at position 18p11.32 in 9% of the patients screened that was of particular interest. Further investigation is necessary to fully understand the role of these variants in CRC risk given the high prevalence among the patients screened. Crown Copyright (C) 2016 Published by Elsevier B.V.