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Science 14 September 2007:
Vol. 317. no. 5844, p. 1500
DOI: 10.1126/science.1138773
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Technical Comments

Response to Comments on "The Consensus Coding Sequences of Human Breast and Colorectal Cancers"

Giovanni Parmigiani,1* Jimmy Lin,1 Simina M. Boca,1 Tobias Sjöblom,1 Siân Jones,1 Laura D. Wood,1 D. Williams Parsons,1 Thomas Barber,1,2 Phillip Buckhaults,3 Sanford D. Markowitz,4 Ben Ho Park,5 Kurtis E. Bachman,6 Nickolas Papadopoulos,1 Bert Vogelstein,1* Kenneth W. Kinzler,1* Victor E. Velculescu1*

Forrest and Cavet, Getz et al., and Rubin and Green describe a variety of statistical methods to analyze the mutational data published in Sjöblom et al. However, their conclusions are inaccurate because they are based on analyses that do not fully take into account the experimental design and other critical features of our study. When these factors are incorporated, their methods provide estimates similar to those we reported and support the conclusion that a large number of genes are mutated at rates greater than the passenger mutation rate.

1 Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute and Departments of Biostatistics and Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
2 Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
3 Department of Pathology and Microbiology, Center for Colon Cancer Research, and The South Carolina Cancer Center, Division of Basic Research, University of South Carolina, School of Medicine, Columbia, SC 29229, USA.
4 Department of Medicine and Ireland Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, and Howard Hughes Medical Institute, Cleveland, OH 44106, USA.
5 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA.
6 Departments of Radiation Oncology and Biochemistry and Molecular Biology, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

* To whom correspondence should be addressed. E-mail: gp{at}jhu.edu (G.P.); vogelbe{at}jhmi.edu (B.V.); kinzlke{at}jhmi.edu (K.W.K.); velculescu{at}jhmi.edu (V.E.V.)

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Science. ISSN 0036-8075 (print), 1095-9203 (online)