Masson Amy L, Talseth-Palmer Bente A, Evans Tiffany-Jane, McElduff Patrick, Spigelman Allan D, Hannan Garry N, Scott Rodney J
Centre for Information-Based Medicine, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, 2305, Australia; School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, New South Wales, 2308, Australia.
Centre for Public Health, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, 2305, Australia; School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, New South Wales, 2308, Australia.
Meta Gene. 2015 Dec 24;7:95-104. doi: 10.1016/j.mgene.2015.12.005. eCollection 2016 Feb.
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 ~ 80% polyposis patients with FAP. In the remaining 20% no genetic diagnosis can be provided suggesting other genes or mechanisms 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.
家族性腺瘤性息肉病（FAP）是结直肠癌（CRC）第二常见的遗传易感性疾病，与结肠和直肠中数百至数千个腺瘤的发生相关。约80%的FAP息肉病患者存在APC基因突变。在其余20%的患者中无法进行基因诊断，这表明可能是其他使APC失活的基因或机制导致了疾病。拷贝数变异（CNV）在FAP中仍有待研究，可能在一部分息肉病患者的疾病发生中起作用。使用270万个探针的微阵列（Affymetrix）对56例息肉病患者和40例对照进行CNV筛查，并使用ChAS（Affymetrix）分析数据。在息肉病队列中总共鉴定出142个独特的CNV，表明它们与CRC风险有关。我们在CRC易感基因APC、DCC、MLH1和CTNNB1中，在4例不相关的息肉病患者中特别鉴定出CNV，这些CNV可能促成了这些患者的疾病发展。在9%的筛查患者中，在18p11.32位置观察到一个反复出现的缺失，这一情况特别令人关注。鉴于在筛查患者中该缺失的高发生率，有必要进行进一步研究以充分了解这些变异在CRC风险中的作用。
