Accumulation of p53 protein is frequent in ovarian cancers associated with BRCA1 and BRCA2 germline mutations.
Accumulation of p53 protein is frequent in ovarian cancers associated with BRCA1 and BRCA2 germline mutations.
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p53 蛋白的积累在与 BRCA1 和 BRCA2 种系突变相关的卵巢癌中很常见。
DOI：
10.1136/jcp.52.5.372
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发表时间：
1999
影响因子：
3.4
通讯作者：
Jacobs,IJ
中科院分区：
文献类型：
--
作者：
Zweemer,RP;Shaw,PA;Verheijen,RM;Ryan,A;Berchuck,A;Ponder,BA;Risch,H;McLaughlin,JR;Narod,SA;Menko,FH;Kenemans,P;Jacobs,IJ
高达95%的遗传性卵巢癌病例是由BRCA1或BRCA2基因突变引起的。这两个基因都是肿瘤抑制基因，癌症的发展被认为除了遗传的种系易感性外，还需要体细胞遗传事件的积累。目前尚不清楚BRCA相关卵巢癌的这些体细胞事件是否与散发病例相似或不同。卵巢癌中最常见的体细胞遗传事件是p53基因的突变。目的研究p53在遗传性卵巢癌中的作用，通过分析发生在BRCA1或BRCA2种系突变携带者的卵巢癌中p53蛋白的积累，并将结果与BRCA1和BRCA2均阴性的卵巢癌患者的一组结果进行比较。方法研究对象为39例既往证实有BRCA突变的卵巢癌患者。采用标准微波抗原提取技术对档案组织进行p53免疫组化。将p53积累率与40例BRCA1和BRCA2种系突变检测为阴性的卵巢癌病例进行比较。结果在BRCA相关卵巢癌和BRCA阴性对照中，tsp53的积累相似。总体而言，39例BRCA1或BRCA2阳性病例中有27例（69%）有p53积累的证据，而40例浸润性卵巢癌病例中有24例（60%）BRCA1和BRCA2种系突变检测为阴性。BRCA1相关卵巢癌30例中有22例（73%）显示p53积累；9例BRCA2相关卵巢癌中有5例存在p53积累。结论除了种系BRCA1和BRCA2突变外，体细胞p53改变导致p53积累是遗传性卵巢癌的重要事件，其发生率与非brca相关卵巢癌相同。
BACKGROUNDMutations in the BRCA1 or BRCA2 genes are responsible for up to 95% of hereditary ovarian cancer cases. Both genes function as tumour suppressor genes, and development of a cancer is thought to require an accumulation of somatic genetic events in addition to the inherited germline predisposition. It is unknown whether these somatic events in BRCA associated ovarian cancer are similar to or distinct from those in sporadic cases. The most frequent somatic genetic event in ovarian cancer is a mutation of the p53 gene.AIMTo study the role of p53 in hereditary ovarian cancer, by analysing accumulation of the p53 protein in ovarian cancers which occurred in BRCA1 or BRCA2 germline mutation carriers and comparing the results with a panel of ovarian cancers from patients who tested negative for both BRCA1 and BRCA2.METHODSThe study group consisted of 39 ovarian cancer patients in whom a BRCA mutation had been confirmed previously. p53 Immunohistochemistry was performed on archival tissue using a standard microwave antigen retrieval technique. The rate of p53 accumulation was compared with 40 ovarian cancer cases who tested negative for BRCA1 and BRCA2 germline mutations.RESULTSP53 Accumulation was similar in BRCA related ovarian cancers and BRCA negative controls. Overall 27 of 39 BRCA1 or BRCA2 positive cases (69%) had evidence of p53 accumulation, compared with 24 of 40 invasive ovarian cancer cases (60%) which tested negative for BRCA1 and BRCA2 germline mutations. BRCA1 related ovarian cancers showed p53 accumulation in 22 of 30 cases (73%); p53 accumulation was present in five of nine BRCA2 related ovarian cancers.CONCLUSIONSIn addition to germline BRCA1 and BRCA2 mutations, somatic p53 alterations leading to p53 accumulation are an important event in hereditary ovarian cancer and are as frequent as in non-BRCA-related ovarian cancer.
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女佣的膝盖。
DOI：
10.1016/s0140-6736(02)95994-5
发表时间：
1838
期刊：
The Lancet
影响因子：
--
作者：
Wm. Lambton
通讯作者：
Wm. Lambton
影响因子：
158.5
作者：
Stratton, JF;Gayther, SA;Ponder, BAJ
通讯作者：
Ponder, BAJ
三十个卵巢癌家族的临床和遗传评估。
影响因子：
9.8
作者：
R. Zweemer;R. Verheijen;J. Gille;P. V. van Diest;G. Pals;F. Menko
通讯作者：
F. Menko
p53 抑癌基因在妇科癌症中经常发生改变
影响因子：
3.8
作者：
A. Berchuck;M. F. Kohler;J. Marks;R. Wiseman;J. Boyd;R. Bast
通讯作者：
R. Bast
影响因子：
9.8
作者：
Ford, D;Easton, DF;Vasen, H
通讯作者：
Vasen, H