Zhong X, Hemmi H, Koike J, Tsujita K, Shimatake H
Hum Mutat. 2000 Mar;15(3):296-7. doi: 10.1002/(SICI)1098-1004(200003)15:3<296::AID-HUMU18>3.0.CO;2-X.
The E2F family of transcription factors regulates the expression of genes required for DNA synthesis and cell cycle control. The AGC triplet repeat in the coding region of the E2F-4 gene, a member of the family, has been reported to be mutated in colorectal cancers with a microsatellite instability (MSI) phenotype. We found a wider range variation of the repeat number in DNAs from tumors, the corresponding normal mucosa, and healthy individuals. A total of 5 repeat variants, ranging from 8 to 17 AGC repeats, was detected in 6 (9.7%) of the 62 healthy individuals and 8 (8.9%) of the 90 normal DNAs of the patients. The wild-type 13 repeat was present in all of these individuals. The variation of the AGC repeat number may be a polymorphism. Further, loss of heterozygosity (LOH) at the E2F-4 locus in the tumor tissues of 2 (25%) of the 8 informative cases was detected. The variation may be a useful marker for detection of LOH in primary tumors.
E2F转录因子家族调控DNA合成及细胞周期控制所需基因的表达。据报道，该家族成员E2F-4基因编码区的AGC三联体重复序列在具有微卫星不稳定性（MSI）表型的结直肠癌中发生了突变。我们发现肿瘤、相应正常黏膜及健康个体的DNA中，该重复序列的数目存在更广泛的变异。在62名健康个体中的6名（9.7%）以及90份患者正常DNA中的8份（8.9%）中，共检测到5种重复变异体，其AGC重复次数从8次到17次不等。所有这些个体均存在野生型的13次重复。AGC重复数目的变异可能是一种多态性。此外，在8例信息充分的病例中，有2例（25%）肿瘤组织的E2F-4基因座发生了杂合性缺失（LOH）。这种变异可能是检测原发性肿瘤中LOH的有用标志物。
