LINE-1 的低甲基化与头颈部鳞状细胞癌的着丝粒不稳定有关，而不是着丝粒 SAT-α。
Hypomethylation of LINE-1, and not centromeric SAT-α, is associated with centromeric instability in head and neck squamous cell carcinoma.
机构信息
Department of Otolaryngology, Instituto Universitario de Oncología del Principado de Asturias, Hospital Universitario Central de Asturias, Oviedo, Spain.
出版信息
Cell Oncol (Dordr). 2012 Aug;35(4):259-67. doi: 10.1007/s13402-012-0085-5. Epub 2012 Jun 21.
BACKGROUND
Head and neck squamous cell carcinoma (HNSCC) is a tumour type that generally carries very complex chromosomal aberrations. An interesting feature is the elevated occurrence (58 %) of whole arm translocations and isochromosomes, resulting from breakage and illegitimate recombination in centromeric or pericentromeric regions. We hypothesized that alterations in DNA methylation may play a role in the breakage of centromeric repeat sequences in these tumours.
METHODS
We studied the DNA methylation status of global repeats (LINE-1), subtelomeric repeats (D4Z4) and centromeric repeats (SAT-α) in relation to centromeric instability in a series of HNSCC cancer cell lines and primary tumours. We analysed the methylation status by pyrosequencing and the chromosomal aberrations by microarray CGH.
RESULTS
We found a significant association between centromeric instability and hypomethylation of LINE-1, but not D4Z4 and SAT-α.
CONCLUSION
These data suggest that centromeric instability is associated with genomic DNA hypomethylation only when occurring at specific DNA repeat sequences.
背景
头颈部鳞状细胞癌（HNSCC）是一种通常具有非常复杂染色体畸变的肿瘤类型。一个有趣的特征是整条臂易位和等臂染色体的发生率升高（58%），这是由于着丝粒或着丝粒周围区域的断裂和非法重组所致。我们假设 DNA 甲基化的改变可能在这些肿瘤的着丝粒重复序列的断裂中起作用。
方法
我们研究了一系列 HNSCC 癌细胞系和原发性肿瘤中与着丝粒不稳定相关的全球重复序列（LINE-1）、端粒重复序列（D4Z4）和着丝粒重复序列（SAT-α）的 DNA 甲基化状态。我们通过焦磷酸测序分析甲基化状态，通过微阵列 CGH 分析染色体畸变。
结果
我们发现着丝粒不稳定与 LINE-1 的低甲基化显著相关，但与 D4Z4 和 SAT-α 无关。
结论
这些数据表明，只有在特定的 DNA 重复序列中发生时，着丝粒不稳定才与基因组 DNA 低甲基化相关。
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