Wynn H. Kao, Adam I. Riker, Deepa S. Kushwaha, Kimberly Ng, Steven A

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Upregulation of Fanconi Anemia DNA Repair Genes in Melanoma Compared with Non- Melanoma Skin Cancer Wynn H. Kao, Adam I. Riker, Deepa S. Kushwaha, Kimberly Ng, Steven A. Enkemann, Richard Jove, Ralf Buettner, Pascal O. Zinn, Néstor P. Sánchez, Jaime L. Villa, Alan D. D'Andrea, Jorge L. Sánchez, Richard D. Kennedy, Clark C. Chen, Jaime L. Matta Journal of Investigative Dermatology Volume 131, Issue 10, Pages 2139-2142 (October 2011) DOI: 10.1038/jid.2011.181 Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Fanconi anemia, but not nucleotide-excision repair (NER), genes are transcriptionally upregulated in melanoma compared with normal skin and non-melanoma skin cancer (NMSC). (a) Microarray analysis of Fanconi anemia and NER gene expression in metastatic melanoma and squamous cell carcinoma (SCC). Green and red represent decreased and increased expression relative to control, respectively. Color intensity is proportional to expression level up to a 4-fold difference from control. Middle row shows combined expression of FANCD2+FANCL relative to normal skin; dark brown, medium tan, and orange denote 25–50% greater, 50–100% greater, and more than 100% greater than normal, respectively. (b) DNA microarray analysis of Fanconi anemia (FA) and NER genes in primary cutaneous melanoma (PCM). (c) Quantitative reverse transcription PCR analysis of FANCD2 expression in PCM versus NMSC. FANCD2 expression levels were normalized to β-actin mRNA levels. Vertical bars represent standard error. MIS, melanomas in situ. Journal of Investigative Dermatology 2011 131, 2139-2142DOI: (10.1038/jid.2011.181) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Strong nuclear FANCD2 protein expression is observed in primary melanoma but not non-melanoma skin cancer (NMSC). Paraffin-embedded tumors were immunostained with 1:50 anti-FANCD2 (H-300; sc28194, Santa Cruz, Santa Cruz, CA) and then biotinylated anti-rabbit antibody (Vector Laboratories, Burlingame, CA). (a) Photomicrographs of FANCD2 protein expression in primary cutaneous melanoma (PCM; left panels) and NMSC (right panels). Breslow thickness is shown for each PCM. Black bars at lower right of each panel indicate 50μm. (b) Percentage of PCM and NMSC cells with positive nuclear staining for FANCD2 by immunohistochemistry. Numbers associated with each PCM on the horizontal axis represent Breslow thickness. BCC, basal cell carcinoma; SCC, squamous cell carcinoma. Journal of Investigative Dermatology 2011 131, 2139-2142DOI: (10.1038/jid.2011.181) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions