Variable imprinting of H19 and IGF2 in fetal cerebellum and medulloblastoma
Variable imprinting of H19 and IGF2 in fetal cerebellum and medulloblastoma
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DOI：
10.1097/00005072-199612000-00011
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发表时间：
1996-12-01
影响因子：
3.2
通讯作者：
Pietsch, T
中科院分区：
文献类型：
--
作者：
Albrecht, S;Waha, A;Pietsch, T
体细胞中只表达印记基因的母本或父本等位基因。胰岛素样生长因子II（IGF 2）基因和H19基因（一种假定的肿瘤抑制基因）在人类中分别以单等位基因的父系和母系表达进行印记。IGF 2的印记丢失（LOI）（即双等位基因表达）发生在一些肿瘤中，并可能促进肿瘤生长。我们采用聚合酶链反应（PCR）和外显子多态性逆转录-PCR检测了6个胎儿小脑、1个成人小脑、15个髓母细胞瘤和7个髓母细胞瘤细胞系中IGF 2和H19的印迹。IGF 2印迹缺失发生在2/3的胎儿小脑，3/7的髓母细胞瘤，1/4的信息细胞系。4例胎儿小脑、1例成人小脑、4例髓母细胞瘤和1例髓母细胞系中，H19印迹缺失率分别为0/4、0/1、4/4。H19的双等位基因表达仅在两个髓母细胞瘤中部分，然而，一个等位基因明显弱于另一个。IGF 2印迹的缺失发生在髓母细胞瘤或髓母细胞瘤细胞系中，但也可发生在正常胎儿小脑中。因此，它在髓母细胞瘤中的发生可能反映了肿瘤的胚胎性质，而不是主要的发病机制。我们的数据还表明，这两个基因可以印记和表达彼此独立，无论是在正常的小脑和髓母细胞瘤。
Only the maternal or paternal allele of an imprinted gene is expressed in somatic cells. The gene for insulin-like growth factor II (IGF2) and the H19 gene (a putative tumor suppressor gene) are imprinted in humans with monoallelic paternal and maternal expression, respectively. Loss of imprinting (LOI) (i.e. biallelic expression) of IGF2 occurs in some tumors and may promote tumor growth. We examined imprinting of IGF2 and H19 in 6 fetal cerebella, 1 adult cerebellum, 15 medulloblastomas, and 7 medulloblastoma cell lines using polymerase chain reaction (PCR) and reverse transcription-PCR of exonic polymorphisms. Loss of imprinting of IGF2 occurred in 2 out of 3 informative fetal cerebella, 3 out of 7 informative medulloblastomas, and 1 out of 4 informative cell lines. Loss of imprinting of H19 occurred in 0 out of 4 informative fetal cerebella, 0 out of 1 informative adult cerebellum, 4 out of 8 informative medulloblastomas, and 1 out of 4 informative cell lines. The biallelic expression of H19 was only partial in two medulloblastomas, however, with one allele being significantly weaker than the other. Loss of imprinting of IGF2 occurs in medulloblastomas or medulloblastoma cell lines but can also occur in normal fetal cerebellum. Its occurence in medulloblastomas may therefore reflect the tumors' embryonal nature rather than representing a primary pathogenetic mechanism. Our data also indicate that both genes can be imprinted and expressed independently of each another, both in normal cerebellum and medulloblastomas.