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

Oliver A. Hampton, Christopher A. Miller, Maxim Koriabine, Jian Li, Petra Den Hollander, Lucia Carbone, Mikhail Nefedov, Boudewijn F H Ten Hallers, Adrian V. Lee, Pieter J. De Jong, Aleksandar Milosavljevic

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)447-457
Number of pages11
JournalCancer genetics
Volume204
Issue number8
DOIs
StatePublished - Aug 2011

Fingerprint

High-Throughput Nucleotide Sequencing
Genomic Instability
Genome
Breast Neoplasms
Cell Line
Mutation
Genomic Segmental Duplications
Gene Regulatory Networks
Libraries
Neoplasms
Genes

Keywords

  • Copy number variation
  • Fosmid diTag
  • Gene fusion
  • Genomic instability
  • Massively parallel sequencing

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology
  • Medicine(all)

Cite this

Long-range massively parallel mate pair sequencing detects distinct mutations and similar patterns of structural mutability in two breast cancer cell lines. / Hampton, Oliver A.; Miller, Christopher A.; Koriabine, Maxim; Li, Jian; Den Hollander, Petra; Carbone, Lucia; Nefedov, Mikhail; Ten Hallers, Boudewijn F H; Lee, Adrian V.; De Jong, Pieter J.; Milosavljevic, Aleksandar.

In: Cancer genetics, Vol. 204, No. 8, 08.2011, p. 447-457.

Research output: Contribution to journalArticle

Hampton, OA, Miller, CA, Koriabine, M, Li, J, Den Hollander, P, Carbone, L, Nefedov, M, Ten Hallers, BFH, Lee, AV, De Jong, PJ & Milosavljevic, A 2011, 'Long-range massively parallel mate pair sequencing detects distinct mutations and similar patterns of structural mutability in two breast cancer cell lines', Cancer genetics, vol. 204, no. 8, pp. 447-457. https://doi.org/10.1016/j.cancergen.2011.07.009
Hampton, Oliver A. ; Miller, Christopher A. ; Koriabine, Maxim ; Li, Jian ; Den Hollander, Petra ; Carbone, Lucia ; Nefedov, Mikhail ; Ten Hallers, Boudewijn F H ; Lee, Adrian V. ; De Jong, Pieter J. ; Milosavljevic, Aleksandar. / Long-range massively parallel mate pair sequencing detects distinct mutations and similar patterns of structural mutability in two breast cancer cell lines. In: Cancer genetics. 2011 ; Vol. 204, No. 8. pp. 447-457.
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