Analysis of Genomic Imprinting in Human Testicular Tumors

人类睾丸肿瘤的基因组印记分析

基本信息

批准号：
07457370
负责人：
OGAWA Osamu
金额：
$ 3.9万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

Recent molecular analyzes have demonstrated that epigenetic alterations such as genomic imprinting might have an important role in human tumorigenesis in addition to specific genetic alterations. In order to clarify the role of genetic and/or epigenetic alterations in the tumorigenesis of testicular germ cell tumors (GCTs), 42 primary testicular GCTs were analyzed with regard to specific chromosomal losses and their parental origin. High incidence of loss of heterozygosity (LOH) were demonstrated on chromosomes 1p, 3p, 11p, and 17p : 9/19 (47%), 18/39 (46%), 13/40(33%) and 20/36 (56%), respectively. No correlation, however, was found between the frequency of LOH on any chromosomes and clinicopathological features. Regarding the parental origin of the lost allele at these chromosomes, preferential loss was not demonstrated in the present study. To clarify the imprinting status in GCTs, allele-specific expression of H19 gene, which is a paternally imprinted gene on chromosome 11p, was analyzed. All of 11 tumors without LOH at this locus showed biallelic expression of H19. Based on the recent study demonstrating the biallelic expression of H19 in primordial germ cells and spermatogonias in the mouse germ line, these results might suggest that biallelic expression of H19 in testicular GCTs simply reflect the characteristics of original germ cells in which the imprinting marking has been erased and not been newly established rather than because of loss of imprinting during the tumorigenesis.

最近的分子分析表明，除特定的遗传改变外，诸如基因组印迹之类的表观遗传学改变（例如基因组印记）可能在人类肿瘤发生中起重要作用。为了阐明遗传和/或表观遗传学改变在睾丸生殖细胞肿瘤（GCT）的肿瘤发生中的作用，分析了42个原发性睾丸GCT，就特定的染色体损失及其父母起源进行了分析。染色体1p，3p，11p和17p：9/19（47％），18/39（46％），13/40（33％）和20/36（33％）和20/36（56％）在染色体1p，3p，11p和17p：9/19（47％）和17p：9/19（47％）和17p：9/19（47％）和分别证明了杂合性损失的高发病率。然而，在任何染色体上的LOH频率与临床病理学特征之间没有发现相关性。关于这些染色体上失落的等位基因的父母起源，在本研究中没有证明优先损失。为了阐明GCT中的烙印状态，分析了H19基因的等位基因特异性表达，该基因是染色体11p的亲子印象基因。该基因座的所有11个没有LOH的肿瘤中的所有肿瘤均显示出H19的双重表达。基于最近的研究表明，在原始生殖细胞和小鼠生殖系中H19的双重表达，这些结果可能表明，睾丸GCT中H19的双质表达只是反映了原始生殖细胞的特征，这些特征只是擦除了不可接受的标记，而不是新近建立的，而不是因为在tumorigrigrig的损失中而不是新的损失。