Petursdottir Thorgunnur Eyfjord, Thorsteinsdottir Unnur, Jonasson Jon Gunnlaugur, Moller Pall Helgi, Huiping Chen, Bjornsson Johannes, Egilsson Valgardur, Imreh Stefan, Ingvarsson Sigurdur
Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland.
Genes Chromosomes Cancer. 2004 Nov;41(3):232-42. doi: 10.1002/gcc.20072.
A human chromosomal segment regularly lost during tumor formation of microcell hybrids in SCID mice has been mapped to 3p21.3. This segment, called chromosome 3 common eliminated region 1 (C3CER1, also referred to as CER1), may harbor multiple tumor-suppressor genes. Because it was found that similar regions were eliminated in an inter- and intraspecies system and in two tumor types (mouse fibrosarcoma and human renal cell carcinoma), we hypothesized that the importance of C3CER1 would transgress tissue specificity, that is, it could occur in tumors derived from multiple tissues. To evaluate the loss of C3CER1 in various human tumor types, we conducted loss of heterozygosity (LOH) analysis of 576 human solid tumors from 10 different tissues and compared the frequency of deletion in the C3CER1 area to that in two other regions on 3p: the FHIT/FRA3B region, at 3p14.2, and the VHL region, at 3p25.3. Deletions were detected in the C3CER1 region in 83% of informative tumors. Half (47%) the LOH-positive tumors showed LOH at all informative markers, indicating a large deletion. The other half (53%) had a discontinuous LOH pattern, suggesting interstitial deletions or breakpoints. The proportion of tumors with C3CER1 deletions was high in all tumor types investigated, ranging from 70% to 94%, except for the soft-tissue sarcomas (40%). In the VHL and FHIT regions, deletions were observed in 73% and 43%, respectively, of the tumors. Of the three 3p regions analyzed, the highest deletion frequency was observed in the C3CER1 region. Furthermore, we demonstrated that the interstitial deletions including C3CER1 prevail over 3p14.2-pter losses in solid tumors.
在SCID小鼠中微细胞杂种肿瘤形成过程中经常丢失的一段人类染色体片段已被定位于3p21.3。该片段被称为3号染色体共同消除区域1(C3CER1,也称为CER1),可能含有多个肿瘤抑制基因。由于发现在种间和种内系统以及两种肿瘤类型(小鼠纤维肉瘤和人类肾细胞癌)中都存在类似区域的消除,我们推测C3CER1的重要性将超越组织特异性,也就是说,它可能出现在源自多种组织的肿瘤中。为了评估C3CER1在各种人类肿瘤类型中的缺失情况,我们对来自10种不同组织的576例人类实体瘤进行了杂合性缺失(LOH)分析,并将C3CER1区域的缺失频率与3p上的其他两个区域进行了比较:位于3p14.2的FHIT/FRA3B区域和位于3p25.3的VHL区域。在83%的信息性肿瘤中检测到C3CER1区域的缺失。一半(47%)的LOH阳性肿瘤在所有信息性标记处均显示LOH,表明存在大片段缺失。另一半(53%)具有不连续的LOH模式,提示存在间质缺失或断点。在所研究的所有肿瘤类型中,除软组织肉瘤(40%)外,C3CER1缺失的肿瘤比例都很高,范围在70%至94%之间。在VHL和FHIT区域,分别有73%和43%的肿瘤观察到缺失。在分析的三个3p区域中,C3CER1区域的缺失频率最高。此外,我们证明在实体瘤中,包括C3CER1的间质缺失比3p14.2 - pter缺失更为普遍。