Genome Research：癌細(xì)胞中的“混沌”

許多癌細(xì)胞的一個(gè)驚人特征是，它們?nèi)旧w中的DNA混雜在一起。包含多個(gè)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(diǎn)。這種重排可能會(huì)削弱細(xì)胞的調(diào)控系統(tǒng)，因?yàn)檫@可能會(huì)削減基因或?qū)⒒驈目刂扑鼈兓钚缘?/font>DNA區(qū)域中分離開來。

美國(guó)休斯頓貝勒醫(yī)學(xué)院的Oliver A. Hampton和AleksandarMilosavljevic比較了一種乳腺癌細(xì)胞和正常細(xì)胞的基因組，結(jié)果發(fā)現(xiàn)了157處重排。相關(guān)研究論文發(fā)表在《基因組研究》（GenomeResearch）上。

他們的研究結(jié)果反映在上述圖表中。外部環(huán)顯示人類的23對(duì)染色體，第三個(gè)環(huán)中的藍(lán)線顯示內(nèi)部重排，即DNA在同一個(gè)染色體上變換位置。靶心的紅線指明了DNA從一個(gè)染色體向另一個(gè)染色體的轉(zhuǎn)變。

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

相關(guān)閱讀：Science：2008年十大科學(xué)進(jìn)展

創(chuàng)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.