The establishment of primary prevention system of familial ovarian cancer by the analysis of genetic instability.

我们在33个家族性卵巢癌家系中发现了18个个体胚系突变，其中包括16个部位特异性卵巢癌家系和17个乳腺癌家系。突变以无义突变为主；18个突变中有16个突变含有12个移码，6个终止密码子突变，2个错义突变导致锌结合基序缺失或剪接异常。值得注意的是，两个BRCA1突变似乎是日本人独有的，因为T307A和C2919T分别被发现9个和7个家系。在本实验中，我们试图利用覆盖包括X基因在内的整个人类基因组的400个微卫星标记，从34个未检测到BRCA1突变的家族性卵巢癌家系中检测到负责的染色体区域。结果，两点分析软件的结果：基因猎人和多点分析：SIBPAL在3个区域表达高分；2p12-q22(npl评分=2.01，p值=0.0002)、8q22-24(npl评分=2.07，p值=0.0025)和16p12(npl评分=2.03，p值0.0001)。

We found 18 individual germ line mutations in 33 familial ovarian cancer families including 16 site-specific ovarian cancer families and 17 breast ovarian cancer families. The majority of mutations were non-sense mutations ; 16 of 18 mutations were consisted with twelve frame shifts, six stop codon mutations, and two missense mutations causing a loss of zinc-binding motif or splice aberration. Interesting to note, two BRCA1 mutations appear to be unique to Japanese people, since T307A and C2919T were found 9 and 7 families, respectively.In this experiments, we tried to detect responsible chromosomal regions from 34 familial ovarian cancer families in which no BRCA1 mutation was detected by non-parametric linkage analysis using 400 micro satellite markers covering whole human genomes including X gene.As a results, both of analytical soft, two point analysis : GENE HUNTER and multipoint analysis : SIBPAL expressed high scores in 3 regions ; 2p12-q22 ( NPL score=2.01, p value=0.0002),8q22-24 ( NPL=2.07, p value=0.0025) and 16p12 ( NPL score=2.03, p value 0.0001).In next step, we are going to isolate response gene from these 3 regions by case controlled association study using high resolution single nucleotide polymorphism.