Qu G Z, Grundy P E, Narayan A, Ehrlich M
Department of Biochemistry, Tulane Medical School, New Orleans, Louisiana 70112, USA.
Cancer Genet Cytogenet. 1999 Feb;109(1):34-9. doi: 10.1016/s0165-4608(98)00143-5.
Rearrangements in the pericentromeric heterochromatin of chromosome 1 or 16 are often found in many types of cancers, including Wilms tumors, and have been suggested to contribute to oncogenesis or tumor progression. The oncogenic potential of these rearrangements has been ascribed to the resulting chromosome arm imbalances affecting the dosage of tumor suppressor genes or protooncogenes. Because DNA hypomethylation has been linked to rearrangements in the pericentromeric regions of chromosome 1 and 16 in two types of non-cancer cell populations, we examined methylation of normally highly methylated satellite DNA sequences in these regions in Wilms tumors. Hypomethylation was found to be frequent in juxtacentromeric (satellite 2) sequences and, especially, in centromeric (satellite alpha) sequences of chromosome 1. Hypomethylation of satellite 2 DNA of chromosome 16 showed a high degree of concordance with that of satellite 2 DNA of chromosome 1. We discuss the relationship of this satellite DNA hypomethylation in Wilms tumors to chromosome aberrations, as determined by assays for loss of heterozygosity.
1号或16号染色体着丝粒周围异染色质的重排常见于多种癌症，包括肾母细胞瘤，并且有人认为其有助于肿瘤发生或肿瘤进展。这些重排的致癌潜力归因于由此产生的染色体臂失衡，影响了肿瘤抑制基因或原癌基因的剂量。由于在两类非癌细胞群体中，DNA低甲基化与1号和16号染色体着丝粒周围区域的重排有关，因此我们检测了肾母细胞瘤中这些区域正常高度甲基化的卫星DNA序列的甲基化情况。结果发现，着丝粒旁（卫星2）序列，尤其是1号染色体的着丝粒（卫星α）序列中低甲基化现象很常见。16号染色体卫星2 DNA的低甲基化与1号染色体卫星2 DNA的低甲基化高度一致。我们通过杂合性缺失检测，讨论了肾母细胞瘤中这种卫星DNA低甲基化与染色体畸变的关系。
