TY - JOUR
T1 - Long-range massively parallel mate pair sequencing detects distinct mutations and similar patterns of structural mutability in two breast cancer cell lines
AU - Hampton, Oliver A.
AU - Miller, Christopher A.
AU - Koriabine, Maxim
AU - Li, Jian
AU - Den Hollander, Petra
AU - Carbone, Lucia
AU - Nefedov, Mikhail
AU - Ten Hallers, Boudewijn F.H.
AU - Lee, Adrian V.
AU - De Jong, Pieter J.
AU - Milosavljevic, Aleksandar
N1 - Funding Information:
This project was funded by the NIH-NHGRI grant 1 R01 HG02583 and NIH-NCI grants R33 CA114151 and R21 CA128496 to AM.
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
KW - Copy number variation
KW - Fosmid diTag
KW - Gene fusion
KW - Genomic instability
KW - Massively parallel sequencing
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U2 - 10.1016/j.cancergen.2011.07.009
DO - 10.1016/j.cancergen.2011.07.009
M3 - Article
C2 - 21962895
AN - SCOPUS:84856382664
SN - 2210-7762
VL - 204
SP - 447
EP - 457
JO - Cancer Genetics
JF - Cancer Genetics
IS - 8
ER -