Article abstract
Nature Methods 6, 99 - 103 (2008)
Published online: 30 November 2008 | doi:10.1038/nmeth.1276
High-resolution mapping of copy-number alterations with massively parallel sequencing
Derek Y Chiang1,2,5, Gad Getz1,5, David B Jaffe1, Michael J T O'Kelly1, Xiaojun Zhao3, Scott L Carter1,4, Carsten Russ1, Chad Nusbaum1, Matthew Meyerson1,2 & Eric S Lander1
Abstract
Cancer results from somatic alterations in key genes, including point mutations, copy-number alterations and structural rearrangements. A powerful way to discover cancer-causing genes is to identify genomic regions that show recurrent copy-number alterations (gains and losses) in tumor genomes. Recent advances in sequencing technologies suggest that massively parallel sequencing may provide a feasible alternative to DNA microarrays for detecting copy-number alterations. Here we present: (i) a statistical analysis of the power to detect copy-number alterations of a given size; (ii) SegSeq, an algorithm to segment equal copy numbers from massively parallel sequence data; and (iii) analysis of experimental data from three matched pairs of tumor and normal cell lines. We show that a collection of 
14 million aligned sequence reads from human cell lines has comparable power to detect events as the current generation of DNA microarrays and has over twofold better precision for localizing breakpoints (typically, to within 1 kilobase).
- Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
- Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.
- Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
- The Harvard-MIT Division of Health Sciences and Technology, 77 Massachusetts Ave., Cambridge, Massachusetts 02139, USA.
- These authors contributed equally to this work.
Correspondence to: Eric S Lander1 e-mail: lander@broad.mit.edu
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