Identification of a panel of sensitive and specific DNA methylation markers for squamous cell lung cancer

Paul P Anglim^*¹ , Janice S Galler^*¹ , Michael N Koss² , Jeffrey A Hagen³ , Sally Turla² , Mihaela Campan¹ , Daniel J Weisenberger¹ , Peter W Laird¹^,3 , Kimberly D Siegmund⁴ and Ite A Laird-Offringa¹^,3

¹Departments of Surgery and of Biochemistry and Molecular Biology, Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90089-9176, USA

²Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90089-9092, USA

³Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90089-9202, USA

⁴Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90089-9175, USA

author email corresponding author email* Contributed equally

Molecular Cancer 2008, 7:62doi:10.1186/1476-4598-7-62


Published:	10 July 2008

Abstract

Background

Lung cancer is the leading cause of cancer death in men and women in the United States and Western Europe. Over 160,000 Americans die of this disease every year. The five-year survival rate is 15% – significantly lower than that of other major cancers. Early detection is a key factor in increasing lung cancer patient survival. DNA hypermethylation is recognized as an important mechanism for tumor suppressor gene inactivation in cancer and could yield powerful biomarkers for early detection of lung cancer. Here we focused on developing DNA methylation markers for squamous cell carcinoma of the lung. Using the sensitive, high-throughput DNA methylation analysis technique MethyLight, we examined the methylation profile of 42 loci in a collection of 45 squamous cell lung cancer samples and adjacent non-tumor lung tissues from the same patients.

Results

We identified 22 loci showing significantly higher DNA methylation levels in tumor tissue than adjacent non-tumor lung. Of these, eight showed highly significant hypermethylation in tumor tissue (p < 0.0001): GDNF, MTHFR, OPCML, TNFRSF25, TCF21, PAX8, PTPRN2 and PITX2. Used in combination on our specimen collection, this eight-locus panel showed 95.6% sensitivity and specificity.

Conclusion

We have identified 22 DNA methylation markers for squamous cell lung cancer, several of which have not previously been reported to be methylated in any type of human cancer. The top eight markers show great promise as a sensitive and specific DNA methylation marker panel for squamous cell lung cancer.