1Department of Biochemistry and Molecular Biology and the Catherine Birch McCormick Genomics Center, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia; 2The Institution of Chinese-Western Integrative Medicine, Lanzhou University School of Medical Science, Lanzhou, Gansu, China; 3Laboratory of Cellular Hemostasis, Division of Hematology, Center for Biological Evaluation and Research, Food and Drug Administration; 4Laboratory of Clinical Genomics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland; and 5Advanced Biomedical Computing Center, National Cancer Institute-Frederick/Science Applications International Corporation-Frederick, Inc., Frederick, Maryland.
Human malignant melanoma has poor prognosis because of resistance to apoptosis and therapy. We describe identification of the expression profile of 1,037 mitochondria-focused genes and 84 survival-apoptosis genes in 21 malignant melanoma cell lines and 3 normal melanocyte controls using recently developed hMitChip3 cDNA microarrays. Unsupervised hierarchical clustering analysis of 1,037 informative genes, and 84 survival-apoptosis genes, classified these malignant melanoma cell lines into type A (n = 12) and type B (n = 9). Three hundred fifty-five of 1,037 (34.2%) genes displayed significant (P </= 0.030; false discovery rate </= 3.68%) differences (+/->/=2.0-fold) in average expression, with 197 genes higher and 158 genes lower in type A than in type B. Of 84 genes with known survival-apoptosis functions, 38 (45.2%) displayed the significant (P < 0.001; false discovery rate < 0.15%) difference. Antiapoptotic (BCL2, BCL2A1, PPARD, and RAF1), antioxidant (MT3, PRDX5, PRDX3, GPX4, GLRX2, and GSR), and proapoptotic (BAD, BNIP1, APAF1, BNIP3L, CASP7, CYCS, CASP1, and VDAC1) genes expressed at higher levels in type A than in type B, whereas the different set of antiapoptotic (PSEN1, PPP2CA, API5, PPP2R1B, PPP2R1A, and FIS1), antioxidant (HSPD1, GSS, SOD1, ATOX1, and CAT), and proapoptotic (ENDOG, BAK1, CASP2, CASP4, PDCD5, HTRA2, SEPT4, TNFSF10, and PRODH) genes expressed at lower levels in type A than in type B. Microarray data were validated by quantitative reverse transcription-PCR. These results showed the presence of two types of malignant melanoma, each with a specific set of dysregulated survival-apoptosis genes, which may prove useful for development of new molecular targets for therapeutic intervention and novel diagnostic biomarkers for treatment and prognosis of malignant melanoma. [Mol Cancer Ther 2009;8(5):OF1-13].