Long-range massively parallel mate pair sequencing detects distinct mutations and similar patterns of structural mutability in two breast cancer cell lines.

TitleLong-range massively parallel mate pair sequencing detects distinct mutations and similar patterns of structural mutability in two breast cancer cell lines.
Publication TypeJournal Article
Year of Publication2011
AuthorsHampton, OA, Koriabine, M, Miller, CA, Coarfa, C, Li, J, Hollander, PDen, Schoenherr, C, Carbone, L, Nefedov, M, Hallers, BFHTen, Lee, AV, De Jong, PJ, Milosavljevic, A
JournalCancer Genet
Date Published2011 Aug
KeywordsBreast Neoplasms, Cell Line, Tumor, Chromosome Aberrations, Chromosome Mapping, DNA, Neoplasm, Female, Genome, Human, Genomic Instability, High-Throughput Nucleotide Sequencing, Humans, Mutation, Polymerase Chain Reaction, Sequence Analysis, DNA

Cancer genomes frequently undergo genomic instability resulting in accumulation of chromosomal rearrangement. To date, one of the main challenges has been to confidently and accurately identify these rearrangements by using short-read massively parallel sequencing. We were able to improve cancer rearrangement detection by combining two distinct massively parallel sequencing strategies: fosmid-sized (36 kb on average) and standard 5 kb mate pair libraries. We applied this combined strategy to map rearrangements in two breast cancer cell lines, MCF7 and HCC1954. We detected and validated a total of 91 somatic rearrangements in MCF7 and 25 in HCC1954, including genomic alterations corresponding to previously reported transcript aberrations in these two cell lines. Each of the genomes contains two types of breakpoints: clustered and dispersed. In both cell lines, the dispersed breakpoints show enrichment for low copy repeats, while the clustered breakpoints associate with high copy number amplifications. Comparing the two genomes, we observed highly similar structural mutational spectra affecting different sets of genes, pointing to similar histories of genomic instability against the background of very different gene network perturbations.

Alternate JournalCancer Genet
PubMed ID21962895
PubMed Central IDPMC3185296
Grant ListR33 CA114151-03 / CA / NCI NIH HHS / United States
R21 HG004554-01 / HG / NHGRI NIH HHS / United States
1 R01 HG02583 / HG / NHGRI NIH HHS / United States
R33 CA114151-01A1 / CA / NCI NIH HHS / United States
R21 CA128496 / CA / NCI NIH HHS / United States
R33 CA114151-02 / CA / NCI NIH HHS / United States
R21 HG004554-02 / HG / NHGRI NIH HHS / United States
R33 CA114151 / CA / NCI NIH HHS / United States
R01 HG002583-02 / HG / NHGRI NIH HHS / United States
R01 HG002583-03 / HG / NHGRI NIH HHS / United States
R21 HG004554 / HG / NHGRI NIH HHS / United States
R01 HG002583-01 / HG / NHGRI NIH HHS / United States
R01 HG002583 / HG / NHGRI NIH HHS / United States

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