Genomics

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Massive Genomic Rearrangment Acquired in a Single Catastrophic Event During Cancer Development


ABSTRACT: Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina GA massively parallel sequencing technology, we aim to sequence ~1600 microRNAs plus the protein coding genome of 25 matched human renal cancer samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with renal cancer development.Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 25 renal cancers and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 50 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.

PROVIDER: EGAS00000000029 | EGA |

REPOSITORIES: EGA

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Massive genomic rearrangement acquired in a single catastrophic event during cancer development.

Stephens Philip J PJ   Greenman Chris D CD   Fu Beiyuan B   Yang Fengtang F   Bignell Graham R GR   Mudie Laura J LJ   Pleasance Erin D ED   Lau King Wai KW   Beare David D   Stebbings Lucy A LA   McLaren Stuart S   Lin Meng-Lay ML   McBride David J DJ   Varela Ignacio I   Nik-Zainal Serena S   Leroy Catherine C   Jia Mingming M   Menzies Andrew A   Butler Adam P AP   Teague Jon W JW   Quail Michael A MA   Burton John J   Swerdlow Harold H   Carter Nigel P NP   Morsberger Laura A LA   Iacobuzio-Donahue Christine C   Follows George A GA   Green Anthony R AR   Flanagan Adrienne M AM   Stratton Michael R MR   Futreal P Andrew PA   Campbell Peter J PJ  

Cell 20110101 1


Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These  ...[more]

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