Mutational analysis of TP53 and p21 in familial and sporadic ovarian cancer in Japan
Mutational analysis of TP53 and p21 in familial and sporadic ovarian cancer in Japan
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DOI：
10.1016/j.ygyno.2005.09.010
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发表时间：
2006-02-01
影响因子：
4.7
通讯作者：
Tanaka, K
中科院分区：
文献类型：
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作者：
Amikura, T;Sekine, M;Tanaka, K
objective.研究细胞周期检查点基因TP53和p21的体细胞突变是否参与了伴或不伴BRCA1生殖系突变的卵巢癌的发生。我们采用直接测序法对46例BRCA 1生殖系突变的卵巢癌患者和93例散发性卵巢癌患者的TP53和p21基因进行了体细胞遗传学分析。在46例BRCA1病例中的25例和93例散发病例中的40例中检测到TP53体细胞突变（54.3%对43.0%）。相比之下，在46例BRCA1病例中的1例和93例散发病例中的2例中检测到p21体细胞突变（2.2%对2.2%）。散发病例中TP53突变发生在外显子6 - 11的频率高于生殖系BRCA1突变病例（84.4% vs. 56.3%：P = 0.013）。非浆液性肿瘤（如类浆液性、透明细胞性或粘液性）中TP53突变的散发病例比例显著低于浆液性肿瘤（18.5% vs. 53.0%：P = 0.0038）。但在非浆液性和浆液性肿瘤中BRCA 1基因TP53突变的比例无显著性差异（37.5% vs. 57.9%）。我们的研究结果表明，TP53的体细胞突变在散发性非浆液性肿瘤的致癌作用比在散发性浆液性肿瘤或BRCA 1相关肿瘤的作用小。此外，与TP 53体细胞突变相比，p21体细胞突变似乎较少参与卵巢癌的发生。(c)2005年爱思唯尔公司All rights reserved.
Objective. To investigate whether somatic mutations in cell cycle checkpoint genes, TP53 and p21, are involved in the development of ovarian cancer with or without BRCA1 germline mutation.Methods. We analyzed somatic genetic alterations of TP53 and p21 in 46 ovarian cancer patients with BRCA1 germline mutations and 93 sporadic patients, using direct sequencing for the entire coding sequences in TP53 and p21.Results. TP53 somatic mutations were detected in 25 of the 46 BRCA1 cases and 40 of the 93 sporadic cases (54.3% vs. 43.0%). In contrast, p21 somatic mutations were detected in I of the 46 BRCA1 cases and 2 of the 93 sporadic cases (2.2% vs. 2.2%). TP53 mutations in sporadic cases more frequently occurred in exons 6-11 than those in cases with germline BRCA1 mutations (84.4% vs. 56.3%: P = 0.013). The proportion of sporadic cases with TP53 mutations in non-serous tumors (e.g. endometrioid, clear cell, or mucinous) was significantly lower than that in serous tumors (18.5% vs. 53.0%: P = 0.0038). However, there was no significant difference between the proportion of BRCA1 cases with TP53 mutation in non-serous and in serous tumors (37.5% vs. 57.9%).Conclusions. Our results suggest that somatic mutation of TP53 plays less of a role in the carcinogenesis of sporadic non-serous tumors than in that of sporadic serous tumors or BRCA1-related tumors. Furthermore, p21 somatic mutation appears to be less involved in the development of ovarian cancer than TP53 somatic mutation. (c) 2005 Elsevier Inc. All rights reserved.