title: Mutational analysis of TP53 and p21 in familial and sporadic ovarian cancer in Japan.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Science, 1-757 Asahimachi-dori, 951-8510 Niigata City, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Amikura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sekine
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hirai
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hatae
authors.forename: Iwao
authors.initials: I
authors.lastname: Kobayashi
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Fujii
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nagata
authors.forename: Kimio
authors.initials: K
authors.lastname: Ushijima
authors.forename: Koshiro
authors.initials: K
authors.lastname: Obata
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Suzuki
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshinaga
authors.forename: Naohiko
authors.initials: N
authors.lastname: Umesaki
authors.forename: Shinji
authors.initials: S
authors.lastname: Satoh
authors.forename: Takayuki
authors.initials: T
authors.lastname: Enomoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Motoyama
authors.forename: Koji
authors.initials: K
authors.lastname: Nishino
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Haino
authors.forename: Kenichi
authors.initials: K
authors.lastname: Tanaka
mesh_terms: 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*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21