Localization of a novel susceptibility gene for familial ovarian cancer to chromosome 3p22-p25.
We performed genome-wide linkage analysis in 58 patients and nine unaffected members among 28 families with no mutation in BRCA1 or BRCA2, employing a set of 410 microsatellite markers. We initially screened the whole genome, including the X chromosome, by a non-parametric method using the GENEHUNTER program. As a result, chromosome 3p22-p25 showed a suggestive score for linkage [LOD = 3.49 and non-parametric LOD (NPL) = 2.77 at D3S3611] based on a multipoint analysis. Additionally, based on a two-point analysis using dense markers, this 3p22-p25 region showed a P-value < 0.05 at 10 markers and there is suggestive evidence for linkage at two markers within approximately 19 cM (NPL = 2.60 and 2.49 at D3S1597 and D3S3611, respectively). To explore whether the candidate gene in this 3p22-p25 region contributed to carcinogenesis of familial ovarian cancer in a similar fashion to the tumor suppressor gene, we performed loss of heterozygosity (LOH) analysis. It was observed that the frequency of LOH at four markers in this region was >50% only in tumor tissues from patients with no mutation in BRCA1 or BRCA2, not in those with a BRCA1 mutation.
Sekine
M
M
Department of Obstetrics and Gynecology, Niigata University, School of Medicine, Niigata 951-8510, Japan.
Nagata
H
H
Tsuji
S
S
Hirai
Y
Y
Fujimoto
S
S
Hatae
M
M
Kobayashi
I
I
Fujii
T
T
Nagata
I
I
Ushijima
K
K
Obata
K
K
Suzuki
M
M
Yoshinaga
M
M
Umesaki
N
N
Satoh
S
S
Enomoto
T
T
Motoyama
S
S
Tanaka
K
K
D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D014157:Transcription Factors