A sequence-level map of chromosomal breakpoints in the MCF-7 breast cancer cell line yields insights into the evolution of a cancer genome Export

@article{citeulike:3821482, abstract = {10.1101/gr.080259.108 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-p21.1, 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 nonhomologous 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 () and one gene truncation ( or ) 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 (2) involves SULF2, a regulator of cell growth and angiogenesis. We show that knock-down of in cell lines causes tumorigenic phenotypes, including increased proliferation, enhanced survival, and increased anchorage-independent growth.}, author = {Hampton, Oliver A. and Den Hollander, Petra and Miller, Christopher A. and Delgado, David A. and Li, Jian and Coarfa, Cristian and Harris, Ronald A. and Richards, Stephen and Scherer, Steven E. and Muzny, Donna M. and Gibbs, Richard A. and Lee, Adrian V. and Milosavljevic, Aleksandar}, citeulike-article-id = {3821482}, citeulike-linkout-0 = {http://dx.doi.org/10.1101/gr.080259.108}, citeulike-linkout-1 = {http://genome.cshlp.org/content/19/2/167.abstract}, citeulike-linkout-2 = {http://genome.cshlp.org/content/19/2/167.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19056696}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19056696}, day = {9}, doi = {10.1101/gr.080259.108}, issn = {1088-9051}, journal = {Genome Research}, keywords = {breakpoints, breast, cancer, celllines, sequencing}, month = {February}, number = {2}, pages = {167--177}, posted-at = {2009-06-05 01:16:34}, priority = {0}, title = {A sequence-level map of chromosomal breakpoints in the MCF-7 breast cancer cell line yields insights into the evolution of a cancer genome}, url = {http://dx.doi.org/10.1101/gr.080259.108}, volume = {19}, year = {2009} }

TY - JOUR ID - citeulike:3821482 L3 - citeulike-article-id:3821482 N2 - 10.1101/gr.080259.108 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-p21.1, 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 nonhomologous 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 () and one gene truncation ( or ) 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 (2) involves SULF2, a regulator of cell growth and angiogenesis. We show that knock-down of in cell lines causes tumorigenic phenotypes, including increased proliferation, enhanced survival, and increased anchorage-independent growth. IS - 2 JF - Genome Research SN - 1088-9051 EP - 177 TI - A sequence-level map of chromosomal breakpoints in the MCF-7 breast cancer cell line yields insights into the evolution of a cancer genome VL - 19 SP - 167 KW - breakpoints KW - breast KW - cancer KW - celllines KW - sequencing AU - Hampton, Oliver AU - Den Hollander, Petra AU - Miller, Christopher AU - Delgado, David AU - Li, Jian AU - Coarfa, Cristian AU - Harris, Ronald AU - Richards, Stephen AU - Scherer, Steven AU - Muzny, Donna AU - Gibbs, Richard AU - Lee, Adrian AU - Milosavljevic, Aleksandar PY - 2009/02/09/ UR - http://dx.doi.org/10.1101/gr.080259.108 ER -