Abstract: The present invention provides methods for identifying the susceptibility of a cancer cell or population of cells to treatment with Epidermal Growth Factor (EGF) Tyrosine Kinase Inhibitors (TKIs), such as erlotinib. Methods for the in vitro diagnosis of the susceptibility of a tumor in a subject to treatment with TKIs and monitoring tumor susceptibility during treatment are also provided.

Abstract: The invention relates generally to a humanized mouse model and uses thereof. Specifically, the invention relates to methods for generating, maintaining, and expanding a culture of leukocytes in heterologous animals. This invention also relates to use of these animals as models of human immune system for testing molecules in order to treat a disease or disorder such as cancer.

Abstract: In accordance with one or more embodiments, the inventors have conducted the first comprehensive integrated genomic and epigenomic analysis in HNSCC, focusing on identifying genes that have concurrent promoter methylation, mutation and expression downregulation. The intersection of unbiased genome-wide methylation sequencing and methylation array screens uncovered 316 genes, which undergo promoter methylation in HNSCC. Close to 60% concordance was found between concurrent greater promoter methylation and gene downregulation, with PAX1 and PAX5 exhibiting the greatest expression loss. Methods for analyzing tissue samples from a subject for increased risk of poor survival outcomes from HNSCC are provided. Kits for measuring promoter methylation of the genes are also provided.

Abstract: Differentially methylated oral squamous cell carcinoma (OSCC) biomarkers, identified in-vitro and validated in well-characterized surgical specimens, have shown poor clinical correlation in cohorts with different risk profiles. To overcome this lack of relevance we used the HumanMethylation27 BeadChip, publicly available methylation and expression array data, and Quantitative Methylation Specific PCR to uncover differential methylation in OSCC clinical samples with heterogeneous risk profiles. A two stage-design consisting of Discovery and Prevalence screens was used to identify differential promoter methylation and deregulated pathways in patients diagnosed with OSCC and head and neck squamous cell carcinoma. This Phase I Biomarker Development Trial identified a panel of differentially methylated genes in normal and OSCC clinical samples from patients with heterogeneous risk profiles. This panel may be useful for early detection and cancer prevention studies.

Abstract: Methods for the quantifying HPV Trans Renal DNA (TrDNA) from a urine sample from a subject using a dual sequence-capture approach are disclosed. The presently disclosed methods can be used to predict cancers including, but not limited to, cervical, anal, penile, and oropharyngeal cancers.

Abstract: The present invention provides arrays for gene loci that allow diagnosis of cervical cancer in patients who may be asymptomatic or have inconclusive Pap smears or cytology, and allowing earlier diagnosis and treatment of the subject. The present invention also provides methods of determination of a global promoter DNA methylation in a cervical tissue sample from a subject, using a variety of methods which can detect DNA methylation. Further, the invention provides methods of diagnosis of cervical cancer in a subject, by comparing the global promoter DNA methylation in a cervical tissue sample obtained from a subject to the global promoter DNA methylation of standard controls.

Abstract: The present invention provides methods of determination of a global DNA methylation index (GDMI) in a sample from a subject, using a variety of methods which can detect global, genome-wide, and gene-specific DNA methylation to create methylation portraits that can be used for early detection, diagnosis, and clinical management in the personalized medicine space. Further, the invention provides methods of diagnosis of cancer, including gastric cancer and hepatocellular cancer in a subject, by comparing the GDMI in a sample obtained from a subject to the methylation index of standard controls. These methods allow diagnosis of gastric carcinoma and liver cancer in patients who may be asymptomatic or have inconclusive pathology, and allowing earlier treatment of the subject.

Abstract: Pap smears and HPV infection tests do not distinguish between lesions that will progress to an invasive carcinoma and those that will not. We aimed to identify epigenetic biomarkers for diagnosis and progression monitoring of premalignant lesions in cervical cancer. Hypermethylated genes were identified as potential biomarkers after validation by MSP, including GGTLA4 and ZNF516. The methylation frequency for these two genes was higher in tumor: GGTLA4 (100%) and ZNF516 (96%); than in normal samples: GGTLA4 (12%) and ZNF516 (16%). The methylation status of GGTLA4 showed a progression in methylation frequency from normal samples to invasive carcinoma. The immunohistochemical expression was lower in tumor for both: GGTLA4 (50.8%) and ZNF516 (66.2%); than in normal samples: GGTLA4 (71.2%) and ZNF516 (88.1%) (p<0.05). In conclusion, we identified methylation biomarkers for the molecular screening and characterization of cervical cancer.

Abstract: As described in more detail below, the present invention generally features compositions and non-invasive methods useful for the screening, identification, monitoring, or diagnosis of subjects having a neoplasia. The invention further provides highly accurate non-invasive methods for the staging or selection of treatment for a bladder, renal, or prostate cancer in a subject.

Abstract: The present invention provides methods of determination of a global DNA methylation index (GDMI) in a sample from a subject, using a variety of methods which can detect global, genome-wide, and gene-specific DNA methylation to create methylation portraits that can be used for early detection, diagnosis, and clinical management in the personalized medicine space. Further, the invention provides methods of diagnosis of cancer, including gastric cancer and hepatocellular cancer in a subject, by comparing the GDMI in a sample obtained from a subject to the methylation index of standard controls. These methods allow diagnosis of gastric carcinoma and liver cancer in patients who may be asymptomatic or have inconclusive pathology, and allowing earlier treatment of the subject.

Abstract: As described in more detail below, the present invention generally features compositions and non-invasive methods useful for the screening, identification, monitoring, or diagnosis of subjects having a neoplasia. The invention further provides highly accurate non-invasive methods for the staging or selection of treatment for a bladder, renal, or prostate cancer in a subject.

Abstract: We identify markers capable of guiding the decision to incorporate epidermal growth factor receptor (EGFR) inhibitors, in particular EGFR tyrosine kinase inhibitors (TKIs), into chemotherapeutic regimens. Mitogen-inducible gene 6 (Mig6), a negative regulator of EGFR, is selectively upregulated during the development of resistance to the EGFR tyrosine kinase inhibitor (TKI) erlotinib, resulting in decreased EGFR phosphorylation. The ratio of Mig6/EGFR expression highly correlates with erlotinib sensitivity. A low Mig6/EGFR ratio correlates with a high response rate to gefitinib and a marked increase in progression-free survival for patients. The ratio of Mig6 to EGFR is a major predictor of biologic and clinical responses to EGFR inhibitors.

Abstract: Pap smears and HPV infection tests do not distinguish between lesions that will progress to an invasive carcinoma and those that will not. We aimed to identify epigenetic biomarkers for diagnosis and progression monitoring of premalignant lesions in cervical cancer. Hypermethylated genes were identified as potential biomarkers after validation by MSP, including GGTLA4 and ZNF516. The methylation frequency for these two genes was higher in tumor: GGTLA4 (100%) and ZNF516 (96%); than in normal samples: GGTLA4 (12%) and ZNF516 (16%). The methylation status of GGTLA4 showed a progression in methylation frequency from normal samples to invasive carcinoma. The immunohistochemical expression was lower in tumor for both: GGTLA4 (50.8%) and ZNF516 (66.2%); than in normal samples: GGTLA4 (71.2%) and ZNF516 (88.1%) (p<0.05). In conclusion, we identified methylation biomarkers for the molecular screening and characterization of cervical cancer.

Abstract: Differentially methylated oral squamous cell carcinoma (OSCC) biomarkers, identified in-vitro and validated in well-characterized surgical specimens, have shown poor clinical correlation in cohorts with different risk profiles. To overcome this lack of relevance we used the HumanMethylation27 BeadChip, publicly available methylation and expression array data, and Quantitative Methylation Specific PCR to uncover differential methylation in OSCC clinical samples with heterogeneous risk profiles. A two stage-design consisting of Discovery and Prevalence screens was used to identify differential promoter methylation and deregulated pathways in patients diagnosed with OSCC and head and neck squamous cell carcinoma. This Phase I Biomarker Development Trial identified a panel of differentially methylated genes in normal and OSCC clinical samples from patients with heterogeneous risk profiles. This panel may be useful for early detection and cancer prevention studies.

Abstract: The present invention provides methods of determination of a global DNA methylation index (GDMI) in a sample from a subject, using a variety of methods which can detect global, genome-wide, and gene-specific DNA methylation to create methylation portraits that can be used for early detection, diagnosis, and clinical management in the personalized medicine space. Further, the invention provides methods of diagnosis of cancer, including gastric cancer and hepatocellular cancer in a subject, by comparing the GDMI in a sample obtained from a subject to the methylation index of standard controls. These methods allow diagnosis of gastric carcinoma and liver cancer in patients who may be asymptomatic or have inconclusive pathology, and allowing earlier treatment of the subject.

Abstract: The present invention provides methods for aiding in the diagnoses of the neoplastic condition of a lung cell and methods of screening for a potential therapeutic agent for the reversal of the neoplastic condition.

Abstract: The present invention provides methods for aiding in the diagnoses of the neoplastic condition of a lung cell and methods of screening for a potential therapeutic agent for the reversal of the neoplastic condition.

Abstract: The BRAF gene has been found to be activated by mutation in human cancers, predominantly in malignant melanoma. We tested 476 primary tumors, including 214 lung, 126 head and neck, 54 thyroid, 27 bladder, 38 cervical, and 17 prostate cancers, for the BRAF T1796A mutation by polymerase chain reaction (PCR)-restriction enzyme analysis of BRAF exon 15. In 24 (69%) of the 35 papillary thyroid carcinomas examined, we found a missense thymine (T)?adenine (A) transversion at nucleotide 1796 in the BRAF gene (T1796A). The T1796A mutation was detected in four lung cancers and in six head and neck cancers but not in bladder, cervical, or prostate cancers. Our data suggested that activating BGRAF mutations may be an important even in the development of papillary thyroid cancer. Moreover, BRAF mutation reliably predicts a poor prognosis for papillary thyroid carcinomas.

Abstract: The present invention provides methods for aiding in the diagnoses of the neoplastic condition of a lung cell and methods of screening for a potential therapeutic agent for the reversal of the neoplastic condition.

Abstract: A method of identifying epigenetically silenced genes, e.g., methylation silenced genes, in cancer cells is provided. In addition, methods of identifying a cancer by detecting epigenetic silencing of gene expression are provided, as are methods of treating a subject having such a cancer, for example, a colorectal cancer and/or gastric cancer. Reagents for practicing such methods also are provided.