The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers.
The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers.
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DOI：
10.1186/1471-2407-7-152
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发表时间：
2007-08-06
期刊：
影响因子：
3.8
通讯作者：
Friedenson B
中科院分区：
文献类型：
--
作者：
Friedenson B
本研究旨在验证以下假设：含有BRCA 1和BRCA 2蛋白的途径中几乎任何组分的失活都会增加淋巴瘤和白血病的风险。在没有BRCA 1或BRCA 2基因突变的人中，编码的蛋白质可以预防乳腺癌/卵巢癌。然而，BRCA 1和BRCA 2蛋白具有多种功能，包括参与通过无错误方法介导DNA双链断裂修复的途径。由于基因突变，BRCA 1、BRCA 2或该“BRCA途径”中任何其他关键蛋白的失活应该会破坏这种无错误的修复过程。由双链断裂产生的DNA片段然后被留给非特异性过程，这些过程将它们重新连接，而不考虑保留正常的基因调控或功能，因此DNA片段的重排更有可能。这些类型的重排通常与一些淋巴瘤和白血病有关。文献检索产生了大约2500篇与BRCA途径相关的流行病学和基础科学文章。对这些文章进行了审查，并将其复制到数据库中，以便于访问。统计信息的荟萃分析比较了血液系统癌症的风险与含有BRCA 1/2基因产物的模型途径中组分的突变。BRCA通路中几乎任何地方编码蛋白质的基因的有害突变使某些白血病和淋巴瘤的风险增加近2000倍。风险大幅增加的癌症包括套细胞淋巴瘤、急性髓性白血病、急性淋巴细胞白血病、慢性淋巴细胞白血病和幼淋巴细胞白血病。套细胞淋巴瘤是由11号和14号染色体之间互换的DNA片段的特征性重排定义的。DNA易位或重排也发生在其他癌症的显着百分比。BRCA通路的一个重要功能是预防可能涉及非随机特征性基因重排的人类白血病和淋巴瘤亚组。在这里，BRCA通路缺陷中的遗传缺陷是一种染色体错误修复综合征，可能促进这一亚组的体细胞癌。该途径中单个基因的失活可增加多种癌症的风险，并且同一途径中不同基因的失活可能具有类似的效果。这里提出的结果可能有临床意义的监测和治疗。
The present study was designed to test the hypothesis that inactivation of virtually any component within the pathway containing the BRCA1 and BRCA2 proteins would increase the risks for lymphomas and leukemias. In people who do not have BRCA1 or BRCA2 gene mutations, the encoded proteins prevent breast/ovarian cancer. However BRCA1 and BRCA2 proteins have multiple functions including participating in a pathway that mediates repair of DNA double strand breaks by error-free methods. Inactivation of BRCA1, BRCA2 or any other critical protein within this "BRCA pathway" due to a gene mutation should inactivate this error-free repair process. DNA fragments produced by double strand breaks are then left to non-specific processes that rejoin them without regard for preserving normal gene regulation or function, so rearrangements of DNA segments are more likely. These kinds of rearrangements are typically associated with some lymphomas and leukemias. Literature searches produced about 2500 epidemiology and basic science articles related to the BRCA pathway. These articles were reviewed and copied to a database to facilitate access. Meta-analyses of statistical information compared risks for hematologic cancers vs. mutations for the components in a model pathway containing BRCA1/2 gene products. Deleterious mutations of genes encoding proteins virtually anywhere within the BRCA pathway increased risks up to nearly 2000 fold for certain leukemias and lymphomas. Cancers with large increases in risk included mantle cell lymphoma, acute myeloid leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, and prolymphocytic leukemia. Mantle cell lymphoma is defined by a characteristic rearrangement of DNA fragments interchanged between chromosomes 11 and 14. DNA translocations or rearrangements also occur in significant percentages of the other cancers. An important function of the BRCA pathway is to prevent a subgroup of human leukemias and lymphomas that may involve non-random, characteristic gene rearrangements. Here, the genetic defect in BRCA pathway deficiencies is a chromosomal misrepair syndrome that may facilitate this subgroup of somatic cancers. Inactivation of a single gene within the pathway can increase risks for multiple cancers and inactivation of a different gene in the same pathway may have similar effects. The results presented here may have clinical implications for surveillance and therapy.
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影响因子：
8.8
作者：
Evans HS;Lewis CM;Robinson D;Bell CM;Møller H;Hodgson SV
通讯作者：
Hodgson SV
临时细胞性白血病核体的行为是DNA损伤传感器，其对DNA双链断裂的反应由NBS1和激酶ATM，CHK2和ATR调节。
DOI：
10.1083/jcb.200604009
发表时间：
2006-10-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Dellaire G;Ching RW;Ahmed K;Jalali F;Tse KC;Bristow RG;Bazett-Jones DP
通讯作者：
Bazett-Jones DP
影响因子：
20.3
作者：
Kutler, DI;Singh, B;Auerbach, AD
通讯作者：
Auerbach, AD
影响因子：
15.8
作者：
Einarsdottir, Kristjana;Humphreys, Keith;Wedren, Sara
通讯作者：
Wedren, Sara
影响因子：
3.4
作者：
Boultwood, J
通讯作者：
Boultwood, J