Mutational analysis of TP53 and p21 in familial and sporadic ovarian cancer in Japan.
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 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%).


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.
Amikura
Takayuki
T
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Science, 1-757 Asahimachi-dori, 951-8510 Niigata City, Japan.
Sekine
Masayuki
M
Hirai
Yasuo
Y
Fujimoto
Seiichiro
S
Hatae
Masayuki
M
Kobayashi
Iwao
I
Fujii
Tsuneo
T
Nagata
Ichiro
I
Ushijima
Kimio
K
Obata
Koshiro
K
Suzuki
Mitsuaki
M
Yoshinaga
Mitsuhiro
M
Umesaki
Naohiko
N
Satoh
Shinji
S
Enomoto
Takayuki
T
Motoyama
Satoru
S
Nishino
Koji
K
Haino
Kazufumi
K
Tanaka
Kenichi
K
D000328:Adult; D000368:Aged; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D016158:Genes, p53; D018095:Germ-Line Mutation; D006801:Humans; D007564:Japan; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21