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Somatic mutations in cancer are more frequent in heterochromatic and late-replicating regions of the genome. We report that regional disparities in mutation density are virtually abolished within transcriptionally silent genomic regions of cutaneous squamous cell carcinomas (cSCCs) arising in an XPC−/− background. XPC−/− cells lack global genome nucleotide excision repair (GG-NER), thus establishing differential access of DNA repair machinery within chromatin-rich regions of the genome as the primary cause for the regional disparity. Strikingly, we find that increasing levels of transcription reduce mutation prevalence on both strands of gene bodies embedded within H3K9me3-dense regions, and only to those levels observed in H3K9me3-sparse regions, also in an XPC-dependent manner. Therefore, transcription appears to reduce mutation prevalence specifically by relieving the constraints imposed by chromatin structure on DNA repair. We model this relationship among transcription, chromatin state, and DNA repair, revealing a new, personalized determinant of cancer risk.

The availability of whole-exome sequencing has revolutionized the study of genetic disease in recent years, particularly in dermatology, where clinical phenotypes are readily recognized. As this technology becomes increasingly affordable and accessible, questions are emerging regarding the clinical and ethical responsibilities of physicians who determine variants underlying disease, especially with regard to children, for whom treatment may be warranted and clinical course improved based on a known genotype. These responsibilities are accentuated in the developing countries, which harbor most consanguineous populations and thus bear the brunt of monogenic genodermatoses. Although many genetic disorders are identified in these populations, limited educational and clinical infrastructure rarely offers opportunities to improve the course of disease. Here we report a genetic study that illustrates these challenges., (© 2016 Wiley Periodicals, Inc.)

Xeroderma pigmentosum (XP) is a rare, autosomal recessive disease involving a defect in DNA repair leading to the premature development of numerous aggressive cutaneous malignancies. Although atypical fibroxanthoma (AFX) is a neoplasm typically found in the setting of extensive sun exposure or therapeutic radiation, AFXs are rarely associated with children with XP. We report the case of a 13-year-old Guatemalan girl with the XP type C variant who developed one of the largest AFXs reported on a child's finger., (© 2016 Wiley Periodicals, Inc.)

We present four cases of children less than 2 years of age, seen in four different practices, with a similar, unique, and specific presentation of diaper dermatitis, all while using Pampers Baby Dry with Drymax technology. To date, no reported cases exist of allergic contact dermatitis to Pampers Dryweave in medical literature., (© 2012 Wiley Periodicals, Inc.)

Xeroderma pigmentosum (XP) is a group of rare inherited human neurocutaneous diseases, and the group C (XPC) is the major group of patients with XP in Europe, North America, and South America. Current molecular diagnostic methods for XP require specialized, expensive, and time-consuming UV sensitivity and DNA repair assays followed by gene sequencing. To determine whether immunohistochemistry (IHC) would be a robust alternative method to diagnose patients with XPC, we stained sections of paraffin-embedded skin biopsies for XPC by IHC, using 69 archived blocks from confirmed or clinically suspect patients with XPA, XPC, XPD, XPE, and without XP. We found that XPC expression was strong in all skin biopsies from patients without (14 of 14) and other patients with XP (4 of 4), whereas XPC expression was lost in all biopsies from confirmed XPC patients (29 of 29). Patches of strong XPC signal could be detected in sun-damaged skin, squamous and basal cell carcinomas from patients with XPC that colocalized with strong expression of p53 and Ki-67. Patients with XPC can therefore be diagnosed by IHC from paraffin-embedded skin biopsies from regions of skin that are without sun damage or sun-induced tumors. IHC is therefore a robust alternative method to diagnose patients with XPC. This fast and inexpensive method should increase the options for the diagnosis of patients with XPC from paraffin-embedded skin biopsies and could be developed for other complementation groups.