Amikura Takayuki, Sekine Masayuki, Hirai Yasuo, Fujimoto Seiichiro, Hatae Masayuki, Kobayashi Iwao, Fujii Tsuneo, Nagata Ichiro, Ushijima Kimio, Obata Koshiro, Suzuki Mitsuaki, Yoshinaga Mitsuhiro, Umesaki Naohiko, Satoh Shinji, Enomoto Takayuki, Motoyama Satoru, Nishino Koji, Haino Kazufumi, Tanaka Kenichi
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Science, 1-757 Asahimachi-dori, 951-8510 Niigata City, Japan.
Gynecol Oncol. 2006 Feb;100(2):365-71. doi: 10.1016/j.ygyno.2005.09.010. Epub 2005 Dec 9.
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.
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.
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 1 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%).
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.
研究细胞周期检查点基因TP53和p21的体细胞突变是否参与伴有或不伴有BRCA1种系突变的卵巢癌的发生发展。
我们采用直接测序法对46例伴有BRCA1种系突变的卵巢癌患者和93例散发型患者的TP53和p21的整个编码序列进行分析，以检测其体细胞遗传改变。
在46例BRCA1病例中有25例检测到TP53体细胞突变，93例散发型病例中有40例检测到TP53体细胞突变（54.3%对43.0%）。相比之下，46例BRCA1病例中有1例检测到p21体细胞突变，93例散发型病例中有2例检测到p21体细胞突变（2.2%对2.2%）。散发型病例中TP53突变在外显子6-11中出现的频率高于伴有BRCA1种系突变的病例（84.4%对56.3%：P = 0.013）。非浆液性肿瘤（如子宫内膜样癌、透明细胞癌或黏液性癌）中发生TP53突变的散发型病例比例显著低于浆液性肿瘤（18.5%对53.0%：P = 0.0038）。然而，非浆液性和浆液性肿瘤中伴有TP53突变的BRCA1病例比例之间无显著差异（37.5%对57.9%）。
我们的结果表明，TP53体细胞突变在散发型非浆液性肿瘤的致癌过程中所起的作用小于在散发型浆液性肿瘤或BRCA1相关肿瘤中的作用。此外，p21体细胞突变似乎比TP53体细胞突变更少参与卵巢癌的发生发展。
