Global gene expression of histologically normal primary skin cells from BCNS subjects reveals 'single-hit' effects that are influenced by rapamycin

// Amruta Phatak 1 , Mohammad Athar 2 , James A. Crowell 3 , David Leffel 4 , Brittney-Shea Herbert 1 , Allen E. Bale 5 and Levy Kopelovich 6 1 Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA 2 Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA 3 NCI-DCTD-DTP, Bethesda, MD, USA 4 Department of Dermatology, Yale School of Medicine, New Haven, CT, USA 5 Department of Genetics, Yale School of Medicine, New Haven, CT, USA 6 Department of Medicine, Weill Cornell Medical College, New York, NY, USA Correspondence to: Levy Kopelovich, email: kopelovichl@gmail.com Allen E. Bale, email: allen.bale@yale.edu Keywords: Gorlin syndrome; basal cell carcinoma; patched; HH signaling; rapamycin Received: December 09, 2018 Accepted: January 11, 2019 Published: February 15, 2019 ABSTRACT Studies of dominantly heritable cancers enabled insights about tumor progression. BCNS is a dominantly inherited disorder that is characterized by developmental abnormalities and postnatal neoplasms, principally BCCs. We performed an exploratory gene expression profiling of primary cell cultures derived from clinically unaffected skin biopsies of BCNS gene-carriers ( PTCH1 +/- ) and normal individuals. PCA and HC of untreated keratinocytes or fibroblasts failed to clearly distinguish BCNS samples from controls. These results are presumably due to the common suppression of canonical HH signaling in vitro . We then used a relaxed threshold (p-value