ot: The Chaos Inside a Cancer Cell & pdf link

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News link with explanation in plain English (1), followed by an abstract

with link to free-online article (2). An association role for

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*The Chaos Inside a Cancer Cell *

http://www.nytimes.com/2008/12/25/science/25visual.html

" A striking feature of many cancer cells is that the DNA in

their chromosomes is all jumbled up. Chunks of DNA containing one or

more genes have been ripped out of their chromosome and reinserted in a

different place. Other lengths of DNA have been transferred to a

different chromosome altogether... "

*2: *Genome Res. 2008 Dec 9. [Epub ahead of print]

http://genome.cshlp.org/content/early/2008/12/09/gr.080259.108

A sequence-level map of chromosomal breakpoints in the MCF-7

breast cancer cell line yields insights into the evolution of a

cancer genome.

Hampton OA et al.

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.

PMID: 19056696