Abstract: Methods of genomic screening to identify epigenetically silenced genes, including epigenetically silenced tumor suppressor genes are provided. Also provided are methods of detecting a cancer, for example, an esophageal squamous cell carcinoma or a head and neck squamous cell carcinoma, as are methods of treating a subject having such a cancer.

Abstract: We used hierarchical clustering to examine gene expression profiles generated by serial analysis of gene expression (SAGE) in a total of nine normal lung epithelial cells and non-small cell lung cancers (NSCLC). Separation of normal and tumor samples, as well as histopathological subtypes, was evident using the 3,921 most abundant transcript tags. This distinction remained when just 115 highly differentially expressed transcript tags were used. Furthermore, these 115 transcript tags clustered into groups that were suggestive of the unique biological and pathological features of the different tissues examined. Adenocarcinomas were characterized by high-level expression of small airway-associated or immunologically related proteins, while squamous cell carcinomas overexpressed genes involved in cellular detoxification or antioxidation.

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: Two hundred ten markers are provided which are epigenetically silenced in one or more cancer types. The markers can be used diagnostically, prognostically, therapeutically, and for selecting treatments that are well tailored for an individual patient. Restoration of expression of silenced genes can be useful therapeutically, for example, if the silenced gene is a tumor-suppressor gene. Restoration can be accomplished by supplying non-methylated copies of the silenced genes or polynucleotides encoding their encoded products. Alternatively, restoration can be accomplished using chemical demethylating agents or methylation inhibitors. Kits for testing for epigenetic silencing can be used in the context of diagnostics, prognostics, or for selecting “personalized medicine” treatments.

Abstract: The present invention relates to the detection of a cell proliferative disorder associated with alterations of microsatellite DNA in a sample. The microsatellite DNA can be contained within any of a variety of samples, such as urine, sputum, bile, stool, cervical tissue, saliva, tears, or cerebral spinal fluid. The invention is a method to detect an allelic imbalance by assaying microsatellite DNA. Allelic imbalance is detected by observing an abnormality in an allele, such as an increase or decrease in microsatellite DNA which is at or corresponds to an allele. An increase can be detected as the appearance of a new allele. In practicing the invention, DNA amplification methods, particularly polymerase chain reactions, are useful for amplifying the DNA. DNA analysis methods can be used to detect such a decrease or increase. The invention is also a method to detect genetic instability of microsatellite DNA.

Abstract: We used hierarchical clustering to examine gene expression profiles generated by serial analysis of gene expression (SAGE) in a total of nine normal lung epithelial cells and non-small cell lung cancers (NSCLC). Separation of normal and tumor samples, as well as histopathological subtypes, was evident using the 3,921 most abundant transcript tags. This distinction remained when just 115 highly differentially expressed transcript tags were used. Furthermore, these 115 transcript tags clustered into groups that were suggestive of the unique biological and pathological features of the different tissues examined. Adenocarcinomas were characterized by high-level expression of small airway-associated or immunologically related proteins, while squamous cell carcinomas overexpressed genes involved in cellular detoxification or antioxidation.

Abstract: Methods for detection of a cell proliferative disorder, such as cancer, are provided utilizing analysis of target mutant nucleic acids in saliva specimens. The presence of the target mutant nucleic acids is indicative of a neoplastic disorder of the lung or the head and neck.

Abstract: Two hundred ten markers are provided which are epigenetically silenced in one or more cancer types. The markers can be used diagnostically, prognostically, therapeutically, and for selecting treatments that are well tailored for an individual patient. Restoration of expression of silenced genes can be useful therapeutically, for example, if the silenced gene is a tumor-suppressor gene. Restoration can be accomplished by supplying non-methylated copies of the silenced genes or polynucleotides encoding their encoded products. Alternatively, restoration can be accomplished using chemical demethylating agents or methylation inhibitors. Kits for testing for epigenetic silencing can be used in the context of diagnostics, prognostics, or for selecting “personalized medicine” treatments.

Abstract: The present invention provides methods and kits useful for detecting neplasia by measuring the methylation level of biomarkers, especially the promoter region of GSTP1 for the detection of prostate adenocarcinoma.

Abstract: Mitochondrial mutations occur as a product of contact of a person with an environmental pollutant. Mitochondrial mutations are readily detectable in body fluids. Measurement of mitochondrial mutations in body fluids can be used as a dosimeter to monitor exposure to the environmental pollutant. Mitochondrial mutations can also be detected in cancer patients. Probes and primers containing mutant mitochondrial sequences can be used to monitor patient condition.

Abstract: The present invention provides methods and kits useful for detecting neplasia by measuring the methylation level of biomarkers, especially the promoter region of GSTP1 for the detection of prostate adenocarcinoma.

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: Methods of detecting progression from precancer to cancer are provided utilizing toluidine blue staining as well as detecting allelic variation at microsatellite loci. An allelic variation in one or more locus is indicative of a progression from precancer to cancer.

Abstract: The invention generally features compositions and methods for the diagnosis and monitoring of a neoplasia (e.g., a prostatic neoplasia) in a subject, as well as methods of treatment selection.

Abstract: We have discovered p40, the shortest variant of a new human p53 homologue (p40/p51/p63/p73H). We have also found that it plays a role in cancer. Low level amplification of the p40 locus accompanied by RNA and protein overexpression was observed in primary lung cancers, and head and neck cancer cell lines. P40 protein overexpression in primary lung tumors was limited to squamous cell carcinoma, tumors known to harbor a high frequency of p53 mutations. Overexpression of p40 in Rat 1a cells led to an increase in soft agar growth and tumor size in mice. We searched for p40 binding proteins using the yeast two-hybrid system. P53 was the most common binding target of the 1.6×106 clones screened from a mouse embryonic library. Moreover, coexpression of p40 and p53 led to a decrease in p53 transcriptional activity. Our results support the notion that p40 plays an oncogenic role in human cancer.

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: Methods for detection of a cell proliferative disorder, such as cancer, are provided utilizing analysis of target mutant nucleic acids in saliva specimens are described. The presence of target mutant nucleic acids is indicative of a neoplastic disorder of the lung or the head and neck.

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 suggest that activating BRAF mutations may be an important event in the development of papillary thyroid cancer. Moreover, BRAF mutation reliably predicts a poor prognosis for papillary thyroid carcinomas.

Abstract: We used hierarchical clustering to examine gene expression profiles generated by serial analysis of gene expression (SAGE) in a total of nine normal lung epithelial cells and non-small cell lung cancers (NSCLC). Separation of normal and tumor samples, as well as histopathological subtypes, was evident using the 3,921 most abundant transcript tags. This distinction remained when just 115 highly differentially expressed transcript tags were used. Furthermore, these 115 transcript tags clustered into groups that were suggestive of the unique biological and pathological features of the different tissues examined. Adenocarcinomas were characterized by high-level expression of small airway-associated or immunologically related proteins, while squamous cell carcinomas overexpressed genes involved in cellular detoxification or antioxidation.

Abstract: The present invention provides methods and kits useful for detecting neplasia by measuring the methylation level of biomarkers, especially the promoter region of GSTP1 for the detection of prostate adenocarcinoma.