1. Acquired resistance to the Hedgehog pathway inhibitor vismodegib due to smoothened mutations in treatment of locally advanced basal cell carcinoma 
Tjinta Brinkhuizen, MD, Marie G. Reinders, MD, Michel van Geel, MD, PhD, Annelot J.L. Hendriksen, MD, Aimée D.C. Paulussen, MD, PhD, Véronique J. Winnepenninckx, MD, PhD, Kristien B. Keymeulen, MD, PhD, Patricia M.M.B. Soetekouw, MD, PhD, Maurice A.M. van Steensel, MD, PhD, Klara Mosterd, MD, PhD 
Journal of the American Academy of Dermatology 
Volume 71, Issue 5, Pages (November 2014)
DOI: /j.jaad
Copyright © 2014 American Academy of Dermatology, Inc. Terms and Conditions

2. Fig 1
Clinical pictures and histologic examination on pretreatment and posttreatment tissue. A, Basal cell carcinoma (BCC) before treatment with vismodegib. B, Complete clinical response 16 weeks after start of treatment. C, Newly developed tumor nodules, 27 weeks after start of treatment. D, Tumor biopsy before treatment with vismodegib, showing infiltrative palisading basaloid cells reaching into the reticular dermis fitting the diagnosis of BCC. E, Biopsy from newly developed tumor nodule after 27 weeks of treatment with vismodegib, showing infiltrative basal cell carcinoma. F, Biopsy of responding tissue after 27 weeks of vismodegib, showing extensive fibrosis with an increased number of fibroblasts, neovascularization, a sparse lymphocytic infiltrate, but no residual BCC. (D-F, Hematoxylin-eosin stain; original magnification ×2.5).
Journal of the American Academy of Dermatology  , DOI: ( /j.jaad )
Copyright © 2014 American Academy of Dermatology, Inc. Terms and Conditions

3. Fig 2
Genomic analysis of PTCH1 coding exons and sequence traces from SMO exon 4 and 5 of resistant tumor tissue. A, The top panel confirms the absence of a germline mutation in buccal swab. The primary tumor and resistant tumor, panel 2 and 4 respectively, both harbor the same splice site mutation (arrows) and skewed nucleotide (arrowhead) distribution (indicative of loss of heterozygosity). In the responding tissue, a PTCH1 mutation could no longer be identified. B, Top panels represent resistant tumor 1 and lower panels resistant tumor 2. Arrows indicate the mutations in either exon 4 (left panels) for resistant tumor 2 or exon 5 (right panels) for resistant tumor 1. If the mutation is present in 1 tumor, it is not in the other and vice versa. Normal tissue, primary tumor, and responding tumor tissue display similar wild type sequence (not shown).
Journal of the American Academy of Dermatology  , DOI: ( /j.jaad )
Copyright © 2014 American Academy of Dermatology, Inc. Terms and Conditions