ABSTRACT
Recent advances in sequencing technology allow genome-scale approaches to cancer mutation discovery. Such data-intensive methods have been applied to cutaneous squamous cell carcinomas (SCCs) and melanomas but have not, to our knowledge, been applied to basal cell carcinomas (BCCs). We used whole-exome sequencing to characterize the mutational landscape of sporadic BCCs. We show that BCCs are the most mutated type of human cancer. Tumors from anatomical regions with chronic UV exposure were associated with higher mutation rates than those with intermittent exposure. The majority of all mutations (75.7%) were UV signature. Using a conventional binomial probability model, several genes were found mutated significantly. However, this model assumes a uniform distribution of mutations throughout the genome. We also used a more stringent approach called InVEx that uses a permutation-based framework to pick drivers from passengers. After correction for multiple hypothesis testing, InVEx identified only PTCH1 (Patched 1) as having a significant functional mutation burden. We also found three genes, STAT5B, CRNKL1, and NEBL, with mutational hot spots at a single base in 3 of 12 tumors sequenced. Our findings support the central role of PTCH1 mutations in BCC genesis. Moreover, our discovery of the uniquely high number of mutations in this tumor may lend insight into its biological behavior.
Subject(s)
Carcinoma, Basal Cell/genetics , Exome/genetics , Gene Expression Regulation, Neoplastic , Genome-Wide Association Study/methods , Models, Genetic , Skin Neoplasms/genetics , Aneuploidy , Gene Dosage/genetics , Humans , Mutation/genetics , Patched Receptors , Patched-1 Receptor , Receptors, Cell Surface/genetics , Tumor Suppressor Protein p53/geneticsABSTRACT
BACKGROUND AND OBJECTIVES: Radiation dermatitis occurs in a majority of patients with breast cancer who receive radiation therapy (RT), causes significant pain, and may necessitate treatment delay. Light emitting diode (LED) photomodulation has been reported to minimize radiation dermatitis. This study sought to further evaluate the efficacy of LED photomodulation in lessening radiation dermatitis. MATERIALS & METHODS: After surgery, patients with breast cancer received LED photomodulation or sham treatments in conjunction with three-dimensional conformal RT. Reactions were evaluated using standardized photographs graded according to National Cancer Institute criteria. RESULTS: In the LED treatment group (n=18), no patients had grade 0 reactions, six (33.3%) had grade 1 reactions, 12 (66.7%) had grade 2 reactions, and none had a grade 3 reaction. In the sham treatment group (n=15), one (6.6%) patient had a grade 0 reaction, four (26.7%) had grade 1 reactions, 9 (60.0%) had grade 2 reactions, and one (6.7%) had a grade 3 reaction. Two (11.1%) patients in the LED treatment group and one (6.7%) in the control group had to interrupt treatment. Differences between groups were not statistically significant. CONCLUSION: LED photomodulation did not reduce the incidence of radiation-induced skin reactions or interruptions in therapy. .
