Open Access Highly Accessed Research article

A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors

Andrey Loboda1, Michael Nebozhyn1, Rich Klinghoffer2, Jason Frazier2, Michael Chastain2, William Arthur2, Brian Roberts2, Theresa Zhang3, Melissa Chenard3, Brian Haines3, Jannik Andersen3, Kumiko Nagashima3, Cloud Paweletz1, Bethany Lynch1, Igor Feldman1, Hongyue Dai2, Pearl Huang4 and James Watters1*

Author Affiliations

1 Department of Molecular Profiling and Research Informatics, Merck Research Laboratories, West Point, Pennsylvania 19486, USA

2 Rosetta Inpharmatics LLC, a wholly-owned subsidiary of Merck & Co., Inc, Seattle, Washington 98109, USA

3 Oncology basic research, Merck Research Laboratories, 33 Avenue Louis Pasteur Boston, MA, USA 02115

4 Oncology, Merck Research Laboratories, North Wales, Pennsylvania, 19454, USA

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BMC Medical Genomics 2010, 3:26  doi:10.1186/1755-8794-3-26

Published: 30 June 2010

Additional files

Additional file 1:

Coherence of RAS pathway signatures. Correlation plots showing the relationship between the "UP" and "DOWN" arms of various RAS pathway signatures. A. Bild et al [9], B. Sweet-Cordero et al [12], C. Blum et al [17], D. The ras pathway signature described in this publication. The Y-axis shows the mean log(10) ratio of the genes within the "DOWN" arm of a signature, and the X-axis shows the mean log(10) ratio of the genes within the "UP" arm of a signature. Each dot represents a tumor in the ExpO lung dataset. If a signature is coherent, a pattern of anti-correlation is expected.

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Additional file 2:

Gene overlap in publicly available datasets. Venn diagram showing the overlap in genes within the 812 gene RAS "superset" that are correlated with one another in publicly available datasets. Datasets are listed, number of samples is shown in parentheses.

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Additional file 3:

RAS signature genes. Genes comprising the RAS signature.

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Additional file 4:

RAS signature coherence. p-value by Fisher exact test for signature coherence

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