Reconstructing tumor amplisomes.
BACKGROUND
Duplication of genomic sequences is a common phenomenon in tumor cells. While many duplications associated with tumors have been identified (e.g. via techniques such as CGH), both the organization of the duplicated sequences and the process that leads to these duplications are less clear. One mechanism that has been observed to lead to duplication is the extraction of DNA from the chromosomes and aggregation of this DNA into small, independently replicating linear or circular DNA sequences (amplisomes). Parts of these amplisomes may later be reinserted back into the main chromosomes leading to duplication. Although amplisomes are known to play an important role in tumorigenesis, their architecture and even size remain largely unknown.


RESULTS
We reconstruct the structure of tumor amplisomes by analyzing duplications in the tumor genome. Our approach relies on recently generated data from End Sequence Profiling (ESP) experiments, which allow us to examine the fine structure of duplications in a tumor on a genome-wide scale. Using ESP data, we formulate the Amplisome Reconstruction Problem, describe an algorithm for its solution, and derive a putative architecture of a tumor amplisome that is the source for duplicated material in the MCF7 breast tumor cell line.
Raphael
Benjamin J
BJ
Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093-0114, USA. braphael@ucsd.edu
Pevzner
Pavel A
PA
D000465:Algorithms; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping / Q000379:methods*; D004270:DNA, Circular / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*
D004270:DNA, Circular; D004273:DNA, Neoplasm