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

• DOI: 10.1101/gr.080259.108
• Publication Date: 2008-12-04T03:13:55Z
• Authors: Oliver A. Hampton; Petra Den Hollander; Christopher A. Mi...; David A. Delgado; Jian Li; Cristian Coarfa; Ronald A. Harris; Stephen Richards; Steven E. Scherer; Donna M. Muzny; Richard A. Gibbs; Adrian V. Lee; Aleksandar Milosa...
• Keywords: Breakpoint; Gene rearrangement; Coding region

By applying a method that combines end-sequence profiling and massively parallel sequencing, we obtained sequence-level map of chromosomal aberrations in the genome MCF-7 breast cancer cell line. A total 157 distinct somatic breakpoints two types, dispersed clustered, were identified. 89 are evenly across genome. majority regions low copy repeats (LCRs), indicating possible role for LCRs chromosome breakage. The remaining 68 form four clusters closely spaced coincide with highly amplified detected by array CGH located 1p13.1-p21.1, 3p14.1-p14.2, 17q22-q24.3, 20q12-q13.33 cytobands. clustered not significantly associated LCRs. Sequences flanking most (95%) breakpoint junctions consistent double-stranded DNA break repair nonhomologous end-joining or template switching. 79 known predicted genes involved rearrangement events, including 10 fusions coding exons from different 77 other rearrangements. Four result novel expressed chimeric mRNA transcripts. One fusion products ( RAD51C-ATXN7 ) one gene truncation BRIP1 BACH1 involve members protein complexes responsible homology-driven breaks. Another ARFGEF2-SULF 2) involves SULF2, regulator growth angiogenesis. We show knock-down SULF2 lines causes tumorigenic phenotypes, increased proliferation, enhanced survival, anchorage-independent growth.