Dana-farber-cancer Institute Inc.

The General Hospital Corporation

Whitehead Institute for Biomedical Research

The Brigham and Women's Hospital, Inc.

William R Sellers

Daniel Arie Haber

Pasi Antero Janne

Matthew Meyerson

Thomas J Lynch

Raffaella Sordella

Jeffrey E Settleman

Daphne Winifred Bell

Juan Guillermo Paez

Bruce E Johnson

Bruce E Johnston

Todd R Golub

David M Livingston

William G Kaelin

Phillip G Febbo

Kenneth N Ross

Erik Flemington

Mark A Rubin

Levi A Garraway

Francesca Demichelis

James A DeCaprio

Disclosed herein are methods and reagents for determining the responsiveness of cancer to an epidermal growth factor receptor (EGFR) targeting treatment. The detection of these mutations will allow for the administration of gefitinib, erlotinib and other tyrosine kinase inhibitors to those patients most likely to respond to the drug.

Method to determine responsiveness of cancer to epidermal growth factor receptor targeting treatments

The present invention is directed to a method for determining the responsiveness of cancer to an epidermal growth factor receptor (EGFR) treatment. In a preferred embodiment, the presence of at least one variance in the kinase domain of the erbB1 gene confers sensitivity to the tyrosine kinase inhibitor gefitinib. Thus, a diagnostic assay for these mutations will allow for the administration of gefitinib, erlotinib and other tyrosine kinase inhibitors to those patients most likely to respond to the drug.

Described are methods for identifying single nucleotide polymorphism (SNPs) that are useful for analyzing genetic samples, and for using said SNPs to determine genetic identity of samples.

Methods for identifying and using SNP panels

Methods identifying prostate cancer, methods for prognosing and diagnosing prostate cancer, methods for identifying a compound that modulates prostate cancer development, methods for determining the efficacy of a prostate cancer therapy, and oligonucleotide microarrays containing probes for genes involved in prostate cancer development are described.

Prostate cancer diagnosis and outcome prediction by expression analysis

We have discovered a nuclear protein in normal human cells, 'retinoblastoma-associated protein 1' ('RBAP-1') that binds directly to the retinoblastoma protein pocket of the underphosphorylated form of the retinoblastoma protein ('RB') and does not bind to phosphorylated RB or to RB with inactivating mutations. The translated RBAP-1 sequence does not resemble other proteins whose sequences are known, and RBAP-1 does not contain a sequence homologous to the transforming element common to viral proteins that bind to the RB pocket. RBAP-1 and the E2F transcription activity have similar DNA-binding specificities and can bind to at least some of the same proteins, such as RB and E4.

Retinoblastoma-associated protein 1 CDNA

We have discovered a nuclear protein in normal human cells, 'retinoblastoma-associated protein 1' ('RBAP-1'), also known as E2F-1, that binds directly to the retinoblastoma protein pocket of the underphosphorylated form of the retinoblastoma protein ('RB') and does not bind to phosphorylated RB or to RB with inactivating mutations. The translated RBAP-1 sequence does not resemble other proteins whose sequences are known, and RBAP-1 does not contain a sequence homologous to the transforming element common to viral proteins that bind to the RB pocket. RBAP-1 and the E2F transcription activity have similar DNA-binding specificities and can bind to at least some of the same proteins, such as RB and E4.

Recombinant retinoblastoma-associated protein 1 (E2F-1) polypeptides and

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Chestnut Hill, MA, United States of America

William R Sellers