许多癌细胞的一个惊人特征是，它们染色体中的DNA混杂在一起。包含多个基因的DNA片段从它们的染色体中被移出并被重新插入另外的位点。这种重排可能会削弱细胞的调控系统，因为这可能会削减基因或将基因从控制它们活性的DNA区域中分离开来。
美国休斯顿贝勒医学院的Oliver A. Hampton和Aleksandar Milosavljevic比较了一种乳腺癌细胞和正常细胞的基因组，结果发现了157处重排。相关研究论文发表在《基因组研究》（Genome Research）上。
他们的研究结果反映在上述图表中。外部环显示人类的23对染色体，第三个环中的蓝线显示内部重排，即DNA在同一个染色体上变换位置。靶心的红线指明了DNA从一个染色体向另一个染色体的转变。
其中一个重排扰乱了基因RAD51C，该基因参与严重染色体断裂（DNA双链断裂）的修复。研究人员称，损伤对DNA双链断裂的修复可能是所有其他重排的一个主要原因。（生物谷Bioon.com）
相关阅读：Science：2008年十大科学进展
生物谷推荐原始出处：
Genome Research，doi：10.1101/gr.080259.108，Oliver A Hampton，Aleksandar Milosavljevic
A sequence-level map of chromosomal breakpoints in the MCF-7 breast cancer cell line yields insights into the evolution of a cancer genome
Oliver A Hampton, Petra Den Hollander, Christopher A Miller, David A Delgado, Jian Li, Cristian Coarfa, Ronald A. Harris, Stephen Richards, Steven E. Scherer, Donna M Muzny, Richard A Gibbs, Adrian V Lee, and Aleksandar Milosavljevic1
Baylor College of Medicine
Abstract
By applying a method that combines end-sequence profiling and massively parallel sequencing, we obtained a sequence-level map of chromosomal aberrations in the genome of the MCF-7 breast cancer cell line. A total of 157 distinct somatic breakpoints of two distinct types, dispersed and clustered, were identified. A total of 89 breakpoints are evenly dispersed across the genome. A majority of dispersed breakpoints are in regions of low copy repeats (LCRs), indicating a possible role for LCRs in chromosome breakage. The remaining 68 breakpoints form four distinct clusters of closely spaced breakpoints that coincide with the four highly amplified regions in MCF-7 detected by array CGH located in the 1p13.1-21.1, 3p14.1-p14.2, 17q22-q24.3, and 20q12-q13.33 chromosomal cytobands. The clustered breakpoints are not significantly associated with LCRs. Sequences flanking most (95%) breakpoint junctions are consistent with double-stranded DNA break repair by non-homologous end-joining or template switching. A total of 79 known or predicted genes are involved in rearrangement events, including 10 fusions of coding exons from different genes and 77 other rearrangements. Four fusions result in novel expressed chimeric mRNA transcripts. One of the four expressed fusion products (RAD51C-ATXN7) and one gene truncation (BRIP1 or BACH1) involve genes coding for members of protein complexes responsible for homology-driven repair of double-stranded DNA breaks. Another one of the four expressed fusion products (ARFGEF2-SULF2) involves SULF2, a regulator of cell growth and angiogenesis. We show that knock-down of SULF2 in cell lines causes tumorigenic phenotypes including increased proliferation, enhanced survival, and increased anchorage-independent growth.
