The Wistar Institute

University of Pennsylvania

Valley Health System

Louise C Showe

Michael Showe

Andrew V Kossenkov

Steven M Albelda

Michael V Nebozhyn

Elena Nikonova

Andrei V Kossenkov

Anil Vachani

Andrey Loboda

Donald O'Rourke

Kiranmai Gumireddy

Luke Macyszyn

Qihong Huang

Dmitri G Negorev

Malik Yousef

Ganepola A Ganepola

Olga V Vladimirova

Ramana V Davuluri

Laszlo Kari

Richard C Harvey

Sharmistha Pal

Yingtao Bi

Gerd G Maul

Ganepola AP Ganepola

Methods and compositions are provided for diagnosing lung cancer in a mammalian subject by use of 7 or more selected genes, e.g., a gene expression profile, from the blood of the subject which is characteristic of disease. The gene expression profile includes 7 or more genes of Table I, Table II, Table III, Table IV or Table IX herein.

Compostions and methods for diagnosing lung cancers using gene expression profiles

Methods and compositions are provided for diagnosing lung cancer in a mammalian subject by use of 10 or more selected genes, e.g., a gene expression profile, from the blood of the subject which is characteristic of disease. The gene expression profile includes 10 or more genes of Table I or Table II herein.

Compositions and methods for diagnosing lung cancers using gene expression profiles

The present invention relates to methods and systems for high risk screening, diagnosis, prognosis, and surveillance of lung cancer. Accordingly, in one aspect, the invention provides a method for diagnosing or evaluating whether a subject has, or is at risk of having, lung cancer such as NSCLS. The method comprises obtaining a first expression level of the AKAP4 gene of a population of cells from the blood of a test subject; and comparing the first expression level with a first predetermined reference value. A difference between the first expression level and first predetermined reference value correlates with a diagnosis or evaluation of a lung cancer.

Method and systems for lung cancer diagnosis

Compositions and methods described herein include somatic cells that are competent for reprogramming and malignant transformation and are characterized by a reduction of the levels of Sp100 in the cells, cells having markers of pluripotent stem cells, and methods for preparing same. Methods for reversably regulating aging or reprogramming to pluripotency in a somatic cell involve modulating the expression of Sp100 therein. Methods and compositions for retarding the growth of or suppressing unwanted cell proliferation involve expressing, inducing expression of, or upregulating, Sp100 in a targeted cell that is undergoing unrestricted proliferation or replication or increasing exposure to Sp100 in the environment or microenvironment of the targeted cell. Also disclosed are methods for treating a proliferative disease or condition by increasing expression or levels of Sp100 in the targeted cell or its environment.

Methods and compositions for regulation of cell aging, carcinogenesis and reprogramming

An isoform-level gene panel is disclosed that can accurately classify a glioblastoma subtype from a tumor sample. Such an isoform level gene panel comprises the 121 to 214 target isoforms identified in Table 1. Also disclosed are reagents for quantitatively detecting the expression or activity of the target isoforms of Table 1 in a patient sample. For example, such ligands can be PCR primer and probes sets. This isoform-level gene panel and reagents for detection of the isoforms are useful in an isoform-level assay for diagnosis of the molecular subtype of a glioblastoma in a patient. The assay employs algorithms and a novel computer program that performs the functions of FIG.. In one aspect, the assay is a high-throughput format.

Methods and compositions for diagnosis of glioblastoma or a subtype thereof

Methods and compositions are provided for diagnosing or detecting a condition, e.g., lung disease in a mammalian subject by use of a micro-RNA expression level or an expression level profile of multiple miRNA in the peripheral blood mononuclear cells (PBMC) of the subject which is characteristic of COPD or NSCLC. Detection of changes in expression in specific miRNA biomarkers from that of a reference sample or miRNA expression profile are correlated with non-small cell lung cancer (NSCLC) and/or COPD and permit differentiation among healthy subjects, subjects with COPD and subjects with adenocarcinoma or squamous cell carcinoma.

Biomarkers in peripheral blood mononuclear cells for diagnosing or detecting lung cancers

Methods and compositions are provided for diagnosing lung cancer in a mammalian subject by use of three or more selected genes, e.g., a gene expression profile, from the peripheral blood mononuclear cells (PBMC) of the subject which is characteristic of disease, a stage of the disease, or enables prognosis of recurrence of disease. The gene expression profile includes three or more genes of Table I, Table II, Table III, Table IV, Table V, Table VI or Table VII herein. Detection of changes in expression in the selected genes forming the gene expression profile from that of a reference gene expression profile are correlated with non-small cell lung cancer (NSCLC). One composition for use in such diagnosis includes three or more PCR primer-probe sets, wherein each primer-probe set amplifies a different polynucleotide sequence from the gene expression profile. Another composition for similar use contains a plurality of polynucleotides immobilized on a substrate, which probes hybridize to three or more gene expression products from genes in the gene expression profile. Still another composition involves detection of the protein expression products of genes from the gene expression profile.

Method for diagnosing lung cancers using gene expression profiles in peripheral blood mononuclear cells

A method of developing a gene expression profile indicative of the presence or stage of a selected a disease, disorder or genetic pathology in a mammalian subject employs penalized discriminant analysis with recursive feature elimination. A method of diagnosing a cancer in a mammalian subject includes the steps of examining a sample containing the subject's immune cells and detecting a variance in the expression of a statistically significant number of genes, e.g., at least 10 non-tumor genes from those same genes in a characteristic disease or healthy gene expression profile. A significant variance in expression of these genes when compared to a gene expression profile, preferably an average gene expression profile of a normal control, or significant similarities to an average gene profile of subjects with cancer, correlates with a specific type of cancer and/or location of tumor.

Method of diagnosis of cancer based on gene expression profiles in cells

The present invention is a method distinguishing between head and neck squamous cell carcinoma and lung squamous cell carcinoma. In particular, a 10-gene classifier has been identified which can be used to distinguish between primary squamous cell carcinoma of the lung and metastatic head and neck squamous cell carcinoma. These genes include CXCL13, COL6A2, SFTPB, KRT14, TSPYL5, TMP3, KLK10, MMP1, GAS1, and MYH2. A panel of one or more of these genes, or proteins encoded thereby, can be used for early diagnosis and selection of an appropriate therapeutic treatment.

Method for distinguishing between head and neck squamous cell carcinoma and lung squamous cell carcinoma

Novel DNA sequences located 5' to the chromosome 11p13 breakpoint are employed as diagnostic probes for breast cancers, T cell leukemias and WAGR associated with chromosome 11 abnormalities. Probe compositions and methods for diganostic assays are provided.

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Media, PA, United States of America

Louise C Showe