1997 Fiscal Year Final Research Report Summary
DETECTION AND CHARACTERIZATION OF FAMILIAL OVARIAN CANCER ASSOCIATED GENE BY LINKAGE ANALYSIS.
| Project/Area Number |
08457437
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | NIIGATA UNIVERSITY |
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Principal Investigator |
TANAKA Kenichi NIIGATA UNIVERSITY,DEPARTMENT OF OBSTETRICS AND GYNECOLOGY,PROFESSOR AND CHAIRMAN, 医学部, 教授 (10126427)
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| Co-Investigator(Kenkyū-buntansha) |
AOKI Yoichi NIIGATA UNIVERSITY,DEPARTMENT OF OBSTETRICS AND GYNECOLOGY,ASSOCIATED PROFESSOR, 医学部, 講師 (40231774)
TAKAKUWA Koichi NIIGATA UNIVERSITY,DEPARTMENT OF OBSTETRICS AND GYNECOLOGY,ASSOCIATED PROFESSOR, 医学部, 講師 (80187939)
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| Project Period (FY) |
1996 – 1997
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| Keywords | FAMILIAL OVARIAN CANCER / BRCA1 GENE / LOH |
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| Research Abstract |
We analyzed the alteration of BRCA1 in DNA obtained from 139 individuals of 17 Japanese site-specific ovarian cancer families and 17 breast-ovarian cancer families. Several germline mutations were detected in 18 families, which consisted of 11 breast-ovarian cancer and 7 site-specific ovarian cancer families, by single-strand conformation polymorphism (SSCP) following direct sequence analysis. The mutations included eleven frameshifts, six nonsense mutations, and one missense mutation causing a loss of zinc-binding motif.
The frequency of LOH at the markers on the BRCA1 gene was 57% (8 of 14 cases) in site-specific ovarian cancer families, 100% (6 of 6 cases) in breast-ovarian cancer families. All tumors of the patients carrying mutation of BRCA1 showed deletion of wild-type alleles implicating BRCA1 as a tumor suppresser gene.
In addition, we analyzed clinical features of twenty-three ovarian cancer patients associated with germline mutations of BRCA1 from 5 site-specific ovarian cancer
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families and 6 breast-ovarian cancer families in Japan. The average age at diagnosis was 51.3 years old (range, 38 to 77). Histological examination revealed 24 serous cyst-adenocarcinoma in 23 patients. In 19 patients with clear clinical records, one patient had stage I disease, 15 had stage III and 3 had stage IV.With stage III of disease, 13 patients treated with cisplatin-containing chemotherapy following tumor reduction surgery showed higher survival rate, as compared with age and treatment courses matched controls (0.802 vs.0.180, the log-rank test : p<0.05). Disase-free intervals of BRCA1 group was also significantly longer than that of sporadic cases (median disease free survival 59.6 vs. 8.3).These results suggest that the clinical outcome of ovarian cancer with germline mutations of BRCA1 appears to be more favorable as compared with sporadic cases. Finally, our statistical model for the inheritance of susceptibility to ovarian cancer was derived from the analysis of 26 patients and 50 pedigrees of 12 families. The expected life time risk of ovarian cancer is about 80% for women with mutations of BRCA1 suggesting that the disease penetrance among pedigrees with germline mutations of the BRCA1 gene expressed substantially high level. Less
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[Publications] Hiroshi Aida, Koichi Takakuwa, Hiroshi Nagata, Ikunosuke Tsuneki, Masashi Takano, Shoji Tsuji, Takeshi Takahashi, Takahiko Sonoda, Masayuki Hatae, Katsuyuki Takahashi, Kazuo Hasegawa, Hideki Mizunuma, Nagayasu Toyoda, Hiroyuki Kamada, Yuichi Torii, Noriyasu Saito, Kohei Tanaka, Michiaki Yakushiji, Tsutomu Araki and Kennichi Tanaka: "Clinical Features of Ovarian Cancer in Japanese Women with Germ-Line Mutations of BRCA1." Clin.Cancer Res.4. 235-240 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Masashi Takano, Hiroshi Aida, Ikunosuke Tsuneki, Koichi Takakuwa, Isao Hasegawa, Hajime Tanaka, Masaaki Saito, Shoji Tsuji, Takahiko Sonoda, Masayuki Hatae, Jui-Tung Chen, Katsuyuki Takahashi, Kazuo Hasegawa, Nagayasu Toyoda, Noriyasu Saito, Michiaki Yakushiji, Tsutomu Araki, and Kenichi Tanaka: "Mutational Analysis of BRCA1 Gene in Ovarian and Breast-ovarian Cancer Families in Japan." Jpn.J.Cancer Res. 88. 407-413 (1997)
Description
「研究成果報告書概要(欧文)」より
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