根據(jù)美國癌癥研究協(xié)會最新期刊Cancer Discovery上發(fā)表的數(shù)據(jù),，ATM基因上的突變可增加胰腺癌的遺傳風(fēng)險。
胰腺癌是一種最病態(tài)的癌癥,，患有這種疾病的人能存活5年的人不到5%,。大約10%的患者來自具多例胰腺癌的家庭。
"有重要理由相信,，這種群集是由于遺傳,，但就這一點，我們沒能夠找到解釋大多數(shù)這種家庭胰腺癌群集的致病基因",，主要作者Alison Klein博士說,，她是約翰霍普金斯Sidney Kimmel綜合癌癥中心腫瘤學(xué)副教授、國家家族性胰腺腫瘤登記處主任,。
Klein和同事們使用包括全基因組和整個外顯子組分析的新一代測序法,，在具有家族性胰腺癌的兩個家族中鑒定出ATM基因的突變。
當(dāng)在一大族患者中檢查到這些初步結(jié)果時,，166個患胰腺癌受試者中有4個存在ATM基因突變,，但是在190個配偶控制組中不存在。
Klein說,，對ATM基因存在的認識可能會導(dǎo)致形成更好的胰腺癌篩查,，其中胰腺癌第四個最常見的癌癥相關(guān)性死亡的原因。然而,，目前還沒有建議的篩查測試,。
許多醫(yī)用用內(nèi)窺鏡檢查法作為胰腺癌的篩查工具,，但是研究人員仍在臨床試驗中評估這一技術(shù)。（生物谷bioon.com）
doi:10.1158/2159-8290.CD-11-0194
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ATM Mutations in Patients with Hereditary Pancreatic Cancer
Nicholas J. Roberts, Yuchen Jiao, Jun Yu, Levy Kopelovich, Gloria M. Petersen,Melissa L. Bondy, Steven Gallinger, Ann G. Schwartz, Sapna Syngal, Michele L. Cote,Jennifer Axilbund, Richard Schulick, Syed Z. Ali, James R. Eshleman,Victor E. Velculescu, Michael Goggins, Bert Vogelstein, Nickolas Papadopoulos,Ralph H. Hruban, Kenneth W. Kinzler, and Alison P. Klein
Abstract Pancreatic cancers are the fourth most-common cause of cancer-related deaths in the Western world, with >200,000 cases reported in 2010. Although up to 10% of these cases occur in familial patterns, the hereditary basis for predisposition in the vast majority of affected families is unknown. We used next-generation sequencing, including whole-genome and whole-exome analyses, and identified heterozygous, constitutional, ataxia telangiectasia mutated (ATM) gene mutations in 2 kindreds with familial pancreatic cancer. Mutations segregated with disease in both kindreds and tumor analysis demonstrated LOH of the wild-type allele. By using sequence analysis of an additional 166 familial pancreatic cancer probands, we identified 4 additional patients with deleterious mutations in the ATM gene, whereas we identified no deleterious mutations in 190 spouse controls (P = 0.046). When we considered only the mostly severely affected families with 3 or more pancreatic cancer cases, 4 deleterious mutations were found in 87 families (P = 0.009). Our results indicate that inherited ATM mutations play an important role in familial pancreatic cancer predisposition. Significance: The genes responsible for the majority of cases of familial pancreatic ductal adenocarcinoma are unknown. We here identify ATM as a predisposition gene for pancreatic ductal adenocarcinoma. Our results have important implications for the management of patients in affected families and illustrate the power of genome-wide sequencing to identify the basis of familial cancer syndromes. Cancer Discovery; 2(1): OF1-OF6. ?2011 AACR.
