Genome Research：癌細胞中的“混沌”

許多癌細胞的一個驚人特征是，它們染色體中的DNA混雜在一起。包含多個基因的DNA片段從它們的染色體中被移出并被重新插入另外的位點。這種重排可能會削弱細胞的調控系統，因為這可能會削減基因或將基因從控制它們活性的DNA區域中分離開來。

美國休斯頓貝勒醫學院的Oliver A. Hampton和AleksandarMilosavljevic比較了一種乳腺癌細胞和正常細胞的基因組，結果發現了157處重排。相關研究論文發表在《基因組研究》（GenomeResearch）上。

他們的研究結果反映在上述圖表中。外部環顯示人類的23對染色體，第三個環中的藍線顯示內部重排，即DNA在同一個染色體上變換位置。靶心的紅線指明了DNA從一個染色體向另一個染色體的轉變。

其中一個重排擾亂了基因RAD51C，該基因參與嚴重染色體斷裂（DNA雙鏈斷裂）的修復。研究人員稱，損傷對DNA雙鏈斷裂的修復可能是所有其他重排的一個主要原因。（創賽新聞中心 canspecsci.com）

相關閱讀：Science：2008年十大科學進展

創賽推薦原始出處：

GenomeResearch，doi：10.1101/gr.080259.108，Oliver AHampton，AleksandarMilosavljevic

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 DenHollander, Christopher A Miller, David A Delgado, Jian Li, CristianCoarfa, Ronald A. Harris, Stephen Richards, Steven E. Scherer,Donna M Muzny, Richard A Gibbs, Adrian V Lee, and AleksandarMilosavljevic1

BaylorCollegeof Medicine

Abstract

By applying a method thatcombines end-sequence profiling and massively parallel sequencing,we obtained a sequence-level map of chromosomal aberrations in thegenome of the MCF-7 breast cancer cell line. A total of 157distinct somatic breakpoints of two distinct types, dispersed andclustered, were identified. A total of 89 breakpoints are evenlydispersed across the genome. A majority of dispersed breakpointsare in regions of low copy repeats (LCRs), indicating a possiblerole for LCRs in chromosome breakage. The remaining 68 breakpointsform four distinct clusters of closely spaced breakpoints thatcoincide with the four highly amplified regions in MCF-7 detectedby array CGH located in the 1p13.1-21.1, 3p14.1-p14.2, 17q22-q24.3,and 20q12-q13.33 chromosomal cytobands. The clustered breakpointsare not significantly associated with LCRs. Sequences flanking most(95%) breakpoint junctions are consistent with double-stranded DNAbreak repair by non-homologous end-joining or template switching. Atotal of 79 known or predicted genes are involved in rearrangementevents, including 10 fusions of coding exons from different genesand 77 other rearrangements. Four fusions result in novel expressedchimeric mRNA transcripts. One of the four expressed fusionproducts (RAD51C-ATXN7) and one genetruncation (BRIP1 or BACH1) involve genes coding for members ofprotein complexes responsible for homology-driven repair ofdouble-stranded DNA breaks. Another one of the four expressedfusion products (ARFGEF2-SULF2) involves SULF2, a regulator of cellgrowth and angiogenesis. We show that knock-down ofSULF2 in cell lines causes tumorigenic phenotypes including increased proliferation, enhanced survival, and increased anchorage-independent growth.