Susceptibility pathways in Fanconi's anemia and breast cancer.
Susceptibility pathways in Fanconi's anemia and breast cancer.
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DOI：
10.1056/nejmra0809889
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发表时间：
2010-05-20
期刊：
影响因子：
--
通讯作者：
D'Andrea AD
中科院分区：
文献类型：
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作者：
D'Andrea AD
对罕见遗传病的研究可以帮助我们深入了解常见疾病的病因和治疗方法。一个例子是罕见的染色体不稳定疾病，Fanconi贫血(FA)。对这种疾病的研究已经阐明了骨髓衰竭、癌症发病机制和化疗耐药的一般机制。FA的主要特征是儿童再生障碍性贫血、对癌症或白血病的易感性以及FA细胞对DNA交联剂的过敏性。有13个FA基因，其中一个基因与众所周知的乳腺癌易感基因BRCA2相同。相应的FA蛋白参与识别和修复受损的DNA。FA基因的失活不仅发生在FA患者中，而且在普通人群的各种癌症中也存在。这些发现对于预测肿瘤对传统抗癌药物、多聚ADP核糖聚合酶1的抑制剂(一种参与DNA修复的酶)以及对其他DNA修复抑制剂的敏感性和耐药性具有广泛的意义。
The study of rare genetic diseases can lead to insights into the cause and treatment of common diseases. An example is the rare chromosomal instability disorder, Fanconi Anemia (FA). Studies of this disease have elucidated general mechanisms of bone marrow failure, cancer pathogenesis, and resistance to chemotherapy. The principal features of FA are aplastic anemia in childhood, susceptibility to cancer or leukemia, and hypersensitivity of FA cells to DNA cross-linking agents. There are thirteen FA genes, and one of these genes is identical to the well known breast cancer susceptibility gene, BRCA2. The corresponding FA proteins cooperate in the recognition and repair of damaged DNA. Inactivation of FA genes occurs not only in FA patients but also in a variety of cancers in the general population. These findings have broad implications for predicting the sensitivity and resistance of tumors to conventional anti-cancer agents, to inhibitors of poly-ADP ribose polymerase 1, an enzyme involved in DNA repair, and to other inhibitors of DNA repair.