[卵巢癌中肿瘤抑制基因p53和BRCA1杂合性缺失的分析]

[Analysis of loss of heterozygosity of the tumor suppressor genes p53 and BRCA1 in ovarial carcinomas].

作者信息

Petrović Bojana, Perović Milica, Novaković Ivana, Atanacković Jasmina, Popović Branka, Luković Ljiljana, Petković Spasoje

机构信息

Klinicki centar Srbije, Institut za ginekologiju i akuserstvo, Beograd.

出版信息

Vojnosanit Pregl. 2006 Sep;63(9):813-8. doi: 10.2298/vsp0609813p.

DOI:10.2298/vsp0609813p

PMID:17039893

Abstract

BACKGROUND/AIM: Among the genes involved in ovarian carcinogenesis, there has been increased interest in tumor-suppressor genes p53 and BRCA1. Both of the genes make control of cell cycle, DNA repair and apoptosis. The p53 is a "genome guardian" inactivated in more than 50% of human cancers, while BRCA1 mutations are found mostly in breast and ovarian cancer. The aim of this investigation was to establish the frequency of loss of heterozygosity (LOH) in the regions of the genes p53 and BRCA1 in ovarian carcinomas, and to analyze the association of LOH with the disease stage and prognosis.

METHODS

We analyzed 20 patients with a confirmed diagnosis of epithelilal ovarian carcinoma. DNA for molecular-genetic analysis was extracted from the tumor tissue and blood as normal tissue of each person. Microsatellite markers of the regions of genes p53 and BRCA1 were amplified by PCR method. The determination of allelic status of microsatellites and detection of LOH was performed after PAA gel electroforesis.

RESULTS

Both of the analyzed microsatellite markers were informative in 13/20 (65%) cases. In the region of gene p53, LOH was established in 4/13 (30.7%) tumors. One of them had histological gradus G1, one had gradus G2, and two of them had gradus G3, while all were with the International Federation of Gynecology and Obstetrics (FIGO) IIIc stage. In the region of gene BRCA1, LOH was detected in 5/13 (38.5%) tumors. Four of them had histological gradus G2, and one had gradus G3, while by the (FIGO) classification one was with stage Ib, one was with stage IIIb, while the three were with stage IlIc. LOH in both of the analyzed regions was detected in one tumor (7.70), with histological gradus G3 and the FIGO IIIc stage.

CONCLUSION

The frequency of LOH in epthelial ovarian carcinomas was 30.7% and 38.5% for p53 and BRCA1 gene regions, respectively. Most of tumors with LOH had histological gradus G2 or G3, and the clinical FIGO stage IIIc, suggesting the association of this occurrence with a later phase of the disease.

摘要

背景/目的：在参与卵巢癌发生的基因中，肿瘤抑制基因p53和BRCA1越来越受到关注。这两个基因都参与细胞周期调控、DNA修复和细胞凋亡。p53是一种“基因组守护者”，在超过50%的人类癌症中失活，而BRCA1突变主要见于乳腺癌和卵巢癌。本研究的目的是确定卵巢癌中p53和BRCA1基因区域杂合性缺失（LOH）的频率，并分析LOH与疾病分期及预后的相关性。

方法

我们分析了20例确诊为上皮性卵巢癌的患者。从肿瘤组织和作为正常组织的血液中提取用于分子遗传学分析的DNA。采用PCR方法扩增p53和BRCA1基因区域的微卫星标记。在聚丙烯酰胺凝胶电泳后进行微卫星等位基因状态的测定和LOH的检测。

结果

在13/20（65%）的病例中，两个分析的微卫星标记均具有信息性。在p53基因区域，4/13（30.7%）的肿瘤检测到LOH。其中1例组织学分级为G1，1例为G2，2例为G3，所有病例均为国际妇产科联盟（FIGO）IIIc期。在BRCA1基因区域，5/13（38.5%）的肿瘤检测到LOH。其中4例组织学分级为G2，1例为G3，按照FIGO分类，1例为Ib期，1例为IIIb期，3例为IIIc期。在1例肿瘤（7.7%）中检测到两个分析区域均存在LOH，其组织学分级为G3，FIGO分期为IIIc期。