The University of North Carolina at Chapel Hill

Genecentric Therapeutics, Inc.

University of Utah Research Foundation

Washington University

British Columbia Cancer Agency Branch

Other

Leland Stanford Junior University

Millennium Pharmaceuticals Limited

Applied Genomics, Inc.

Bioclassifier, LLC

Nanostring Technologies, Inc.

Charles M Perou

Hawazin Faruki

Myla Lai-Goldman

David Neil Hayes

Greg Mayhew

Philip Seth Bernard

Jonathan Serody

Matthew J Ellis

Joel S Parker

Torsten O Nielsen

Karen J Moore

Jerry Kaplan

Philip S Bernard

David Botstein

Patrick O Brown

Douglas T Ross

Brian Z Ring

Sean M Ferree

Elaine R Mardis

Andrew Nobel

Maggie Cheang

Gregory Mayhew

Miguel Martin

Eva Carrasco

Cheng Fan

Rosalia Caballero

Mark Miglarese

Rob Seitz

James Stephen Marron

Jan Matthijs Van De Rijn

Elaine Mardis

Matthew Ellis

Mark R Miglarese

James Justin Storhoff

James Marron

Torsten Nielsen

Methods and compositions are provided for determining a subtype of Muscle Invasive Bladder Cancer (MIBC) in an individual by detecting the expression level of at least one classifier biomarker selected from a group of gene signatures for MIBC. Also provided herein are methods and compositions for determining the response of an individual with a MIBC subtype to a therapy such as immunotherapy.

Methods for subtyping of bladder cancer

Methods and compositions are provided for determining a subtype of lung adenocarcinoma (AD) of an individual by detecting the expression level of at least one classifier biomarker selected from a group of gene signatures for lung adenocarcinoma. Also provided herein are methods and compositions for determining the response of an individual with an adenocarcinoma subtype to a therapy such as immunotherapy.

Methods for subtyping of lung adenocarcinoma

Methods and compositions are provided for determining a subtype of lung squamous cell carcinoma (SQ) of an individual by detecting the expression level of at least one classifier biomarker selected from a group of gene signatures for lung squamous cell carcinoma. Also provided herein are methods and compositions for determining the response of an individual with a squamous cell carcinoma subtype to a therapy such as immunotherapy.

Methods for subtyping of lung squamous cell carcinoma

Methods and compositions are provided for determining a subtype of head and neck squamous cell carcinoma (HNSCC) of an individual by detecting the expression level of at least one classifier biomarker selected from a group of gene signatures for HNSCC. Also provided herein are methods and compositions for determining the response of an individual with a HNSCC subtype to a therapy such as immunotherapy.

Methods for subtyping of head and neck squamous cell carcinoma

Methods and compositions are provided for determining a pan-cancer clustering of cluster assignment (COCA) subtype of a cancer in an individual by detecting the expression level of at least one classifier biomarker selected from a group of classifier biomarkers for COCA subtypes. Also provided herein are methods and compositions for determining the response of an individual with a COCA subtype to a therapy such as immunotherapy.

Detecting cancer cell of origin

Methods and compositions are provided for determining whether an adenocarcinoma or squamous cell carcinoma patient is likely to respond to PARP inhibitor treatment. Specifically, a method of assessing whether a patient's adenocarcinoma (AD) lung cancer subtype is terminal respiratory unit (TRU), proximal inflammatory (PI), or proximal proliferative (PP) or a patient's squamous cell carcinoma (SQ) is primitive, classical, secretory or basal is provided herein. The method entails detecting the levels of classifier biomarkers at the nucleic acid level, in an AD or SQ lung cancer sample obtained from the patient. Based in part on the levels of the classifier biomarkers, the AD lung cancer sample is classified as a TRU, PI, or PP AD sample or the SQ lung cancer sample is classified as primitive, classical, secretory or basal and a determination of whether the patient is likely to respond to PARP inhibitor treatment can be made.

Methods for determining response to PARP inhibitors

Methods and compositions are provided for the molecular subtyping of lung cancer samples. Specifically, a method of assessing whether a patient's lung cancer subtype is adenocarcinoma, squamous cell carcinoma, or a neuroendocrine (encompassing both small cell carcinoma and carcinoid) is provided herein. A method for assessing whether a patient's lung cancer subtype is adenocarcinoma, squamous cell carcinoma, small cell carcinoma or carcinoid lung cancer is also provided. The methods provided herein entail probing the levels of the classifier biomarkers of Table 1-Table 6 or a subset thereof at the nucleic acid level, in a lung cancer sample obtained from the patient. Based in part on the levels of the classifier biomarkers, the lung cancer sample is classified as a particular lung cancer subtype.

Methods for typing of lung cancer

Compositions and methods useful in determining the major morphological types of lung cancer are provided. The methods include detecting expression of at least one gene or biomarker in a sample at the protein or nucleic level. The expression of the gene or biomarker can be indicative of the lung tumor subtype as well as prognostic and predictive for therapeutic response. The compositions and methods provided herein are suited for analysis of gene or biomarker expression at the protein or nucleic acid level in paraffin-embedded tissues.

Molecular diagnosis and typing of lung cancer variants

Methods for classifying and for evaluating the prognosis of a subject having breast cancer are provided. The methods include prediction of breast cancer subtype using a supervised algorithm trained to stratify subjects on the basis of breast cancer intrinsic subtype. The prediction model is based on the gene expression profile of the intrinsic genes listed in Table 1. This prediction model can be used to accurately predict the intrinsic subtype of a subject diagnosed with or suspected of having breast cancer. Further provided are compositions and methods for predicting outcome or response to therapy of a subject diagnosed with or suspected of having breast cancer. These methods are useful for guiding or determining treatment options for a subject afflicted with breast cancer. Methods of the invention further include means for evaluating gene expression profiles, including microarrays and quantitative polymerase chain reaction assays, as well as kits comprising reagents for practicing the methods of the invention.

Method of classifying a breast cancer instrinsic subtype

The application describes methods for screening subjects with breast cancer to determine if the breast cancer will be responsive to a breast cancer therapy including a taxane or a taxane derivative. The application also describes methods for treating subjects with breast cancer by screening them for the likelihood of the effectiveness of treating the cancer with a therapy including a taxane or a taxane derivative and administering the therapy in subjects when it is found that a taxane or a taxane derivative is likely to be effective.

Methods of treating breast cancer with taxane therapy

The application describes methods for screening subjects with breast cancer to determine if the breast cancer will be responsive to a breast cancer therapy including an anthracycline. The application also describes methods for treating subjects with breast cancer by screening them for the likelihood of the effectiveness of treating the cancer with a therapy including anthracycline and administering the therapy in subjects when it is found that anthracycline is likely to be effective.

Methods of treating breast cancer with anthracycline therapy

Compositions and methods useful in determining the major morphological types of lung cancer are provided. The methods include detecting expression of at least one gene or biomarker in a sample. The expression of the gene or biomarker is indicative of the lung tumor subtype. The compositions include subsets of genes that are monitored for gene expression. The gene expression is capable of distinguishing between normal lung parenchyma and the major morphological types of lung cancer. The gene expression and somatic mutation data are useful in developing a complete classification of lung cancer that is prognostic and predictive for therapeutic response. The methods are suited for analysis of paraffin-embedded tissues. Methods of the invention include means for monitoring gene or biomarker expression including PCR and antibody-based detection. The biomarkers of the invention are genes and/or proteins that are selectively expressed at a high or low level in certain tumor subtypes. Biomarker expression can be assessed at the protein or nucleic acid level.

The invention provides a variety of reagents for use in the diagnosis and management of breast cancer. The invention utilizes cDNA microarray technology to identify genes whose expression profile across a large group of tumor samples correlates with that of cytokeratin 5 and cytokeratin 17, markers for basal cells of the normal mammary lactation gland. The invention demonstrates that tumors that express cytokeratin 5/6 and/or 17 have a poor prognosis relative to tumors overall. The invention provides basal marker genes and their expression products and uses of these genes for diagnosis of breast cancer and for identification of therapies for breast cancer. In particular, the invention provides basal marker genes including cadherin3, matrix metalloproteinase 14, and cadherin EGF LAG seven-pass G-type receptor 2. The invention provides antibodies to the polypeptides expressed by these genes and methods of use thereof.

Methods of classifying, diagnosing, stratifying and treating cancer patients and their tumors

Growing community of inventors

Chapel Hill, NC, United States of America

Charles M Perou