Dna methylation markers and methods of use

A method for identifying non-small cell lung cancer metastases in a mammalian subject sample comprising:

• isolating one or more nucleic acids from the mammalian subject sample;
• assaying the one or more nucleic acids to detect nucleic acid hypermethylation of a p16 gene and an H-cadherin gene;
• and
• correlating nucleic acid hypermethylation of the p16 gene and the H-cadherin gene with non-small cell lung cancer metastases.

A method for detecting or diagnosing metastatic non-small cell lung cancer in a mammalian subject identified as having non-small cell lung cancer comprising:

• isolating nucleic acids from a non-small cell lung cancer (NSCLC) tumor or one or more lymph nodes of the mammalian subject;
• assaying the nucleic acids to detect nucleic acid hypermethylation of a p16 gene and an H-cadherin gene, in the NSCLC tumor or the one or more lymph nodes of the mammalian subject, wherein nucleic acid hypermethylation of the p16 gene and the H-cadherin gene is detected using a primer, sequencing, methylation sensitive restriction endonucleases, a nucleic acid probe, PCR allele-specific oligonucleotide probe analysis, or oligonucleotide ligation assays;
• and
• correlating nucleic acid hypermethylation of the p16 gene and the H-cadherin gene with metastatic non-small cell lung cancer.

A method for predicting a recurrence of non-small cell lung cancer in a mammalian subject comprising:

• isolating nucleic acids from a cell or tissue sample of the mammalian subject;
• assaying the one or more nucleic acids to detect nucleic acid hypermethylation of a p16 gene and an H-cadherin gene an H-cadherin gene and an APC gene, an APC gene and a p16 gene, or a RASSF1A gene and a p16 gene in the cell or tissue sample of the subject, wherein nucleic acid hypermethylation of the p16 gene and the H-cadherin gene, the H-cadherin gene and the APC gene, the APC gene and the p16 gene, or the RASSF1A gene and the p16 gene is detected using a primer, sequencing, methylation sensitive restriction endonucleases, a nucleic acid probe, PCR, allele-specific oligonucleotide probe analysis, or oligonucleotide ligation assays;
• and
• correlating nucleic acid hypermethylation of the p16 gene and the H-cadherin gene, the H-cadherin gene and the APC gene, the APC gene and the p16 gene, or the RASSF1A gene and the p16 gene with the recurrence of non-small cell lung cancer.

A method for staging or re-staging a non-small cell lung cancer in a mammalian subject comprising:

• isolating nucleic acids from the mammalian subject;
• assaying the nucleic acids to detect nucleic acid hypermethylation of a p16 gene and an H-cadherin gene, wherein hypermethylation of the p16 gene and the H-cadherin gene is detected using a primer, sequencing, methylation sensitive restriction endonucleases, a nucleic acid probe, PCR allele-specific oligonucleotide probe analysis, or oligonucleotide ligation assays;
• and
• correlating nucleic acid hypermethylation of the p16 gene and the H-cadherin gene with non-small cell lung cancer stage.

A method for determining a prognosis of a mammalian subject identified as having non-small cell lung cancer comprising:

• isolating nucleic acids from the mammalian subject;
• assaying the nucleic acids to detect nucleic acid hypermethylation of a p16 gene and an H-cadherin gene, wherein hypermethylation of the p16 gene and the H-cadherin gene is detected using a primer, sequencing, methylation sensitive restriction endonucleases, a nucleic acid probe, PCR, allele-specific oligonucleotide probe analysis, or oligonucleotide ligation assays;
• and
• correlating nucleic acid hypermethylation of the p16 gene and the H-cadherin gene with the prognosis of the mammalian subject.

A method for predicting a recurrence of a non-small cell lung cancer (NSCLC) in a human subject comprising:

• isolating nucleic acids from a lung tumor or lymph node of the subject;
• assaying the nucleic acids to detect nucleic acid hypermethylation of a p16 gene and an H-cadherin gene;
• and
• correlating the nucleic acid hypermethylation state of the p16 gene and the H-cadherin gene with an increased risk of the recurrence of NSCLC in comparison to control lung tumor tissue samples obtained from human subjects without NSCLC recurrence.