Functional Identification of Cancer-Specific Methylation of CDO1, HOXA9, and TAC1 for the Diagnosis of Lung Cancer
Menée sur des lignées cellulaires et à partir de données issues du projet "The Cancer Genome Atlas", cette étude suggère l'intérêt de mesurer le degré de méthylation de trois gènes (CDO1, HOXA9 et TAC1) pour le diagnostic précoce et la stadification d'un cancer du poumon non à petites cellules
Purpose: Purpose: Non-Small Cell Lung Cancer (NSCLC) is the leading cause of cancer mortality in the world. Novel diagnostic biomarkers may augment both existing NSCLC screening methods as well as molecular diagnostic tests of surgical specimens to more accurately stratify and stage candidates for adjuvant chemotherapy. Hypermethylation of CpG islands is a common and important alteration in the transition from normal tissue to cancer.
Experimental Design: Following previously validated methods for the discovery of cancer-specific hypermethylation changes we treated 8 NSCLC cell lines with the hypomethylating agent deoxyazacitidine or trichostatin A. We validated the findings using a large publically available database and two independent cohorts of primary samples.
Results: We identified >300 candidate genes. Using The Cancer Genome Atlas (TCGA) and employing extensive filtering to refine our candidate genes for the greatest ability to distinguish tumor from normal, we define a three-gene panel, CDO1, HOXA9, and TAC1, which we subsequently validate in two independent cohorts of primary NSCLC samples. This 3-gene panel is 100% specific, showing no methylation in 75 TCGA normal and 7 primary normal samples and is 83-99% sensitive for NSCLC depending on the cohort.
Conclusion: This degree of sensitivity and specificity may be of high value to diagnose the earliest stages of NSCLC. Addition of this 3-gene panel to other previously validated methylation biomarkers holds great promise in both early diagnosis and molecular staging of NSCLC.
Clinical Cancer Research , résumé, 2014