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驈目刂扑鼈兓钚缘腄NA區(qū)域中分離開來,。
美國休斯頓貝勒醫(yī)學(xué)院的Oliver A. Hampton和Aleksandar Milosavljevic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》（Genome Research）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,。（生物谷Bioon.com）
相關(guān)閱讀：Science：2008年十大科學(xué)進(jìn)展
生物谷推薦原始出處：
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.
