Transcription restores DNA repair to heterochromatin, determining regional mutation rates in cancer genomes

SummarySomatic 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

Tonsillectomy as a treatment for psoriasis: A review

Psoriasis is a chronic skin disorder that affects 1% to 3% of the general population worldwide. Streptococcal infection, especially streptococcal pharyngitis, has been shown to be a significant trigger of psoriasis in some patients, possibly by sensitizing T cells to keratin epitopes in the skin. Due to the role of the palatine tonsils as an immunological organ that may generate autoreactive T cells, tonsillectomy has been investigated as a treatment for psoriasis. Tonsillectomy originally gained acceptance in Japan as a treatment for palmoplantar pustulosis, a condition that shares features with pustular psoriasis. Subsequently, tonsillectomy has been used for the treatment of plaque psoriasis and guttate psoriasis. Recently, the first randomized, controlled clinical trial of tonsillectomy was performed. Here, we review the available evidence for the benefit of tonsillectomy as a treatment for palmoplantar pustulosis and psoriasis. We also discuss molecular studies aimed at understanding the role of tonsils in skin disease

Tonsillectomy as a treatment for psoriasis: A review

Psoriasis is a chronic skin disorder that affects 1% to 3% of the general population worldwide. Streptococcal infection, especially streptococcal pharyngitis, has been shown to be a significant trigger of psoriasis in some patients, possibly by sensitizing T cells to keratin epitopes in the skin. Due to the role of the palatine tonsils as an immunological organ that may generate autoreactive T cells, tonsillectomy has been investigated as a treatment for psoriasis. Tonsillectomy originally gained acceptance in Japan as a treatment for palmoplantar pustulosis, a condition that shares features with pustular psoriasis. Subsequently, tonsillectomy has been used for the treatment of plaque psoriasis and guttate psoriasis. Recently, the first randomized, controlled clinical trial of tonsillectomy was performed. Here, we review the available evidence for the benefit of tonsillectomy as a treatment for palmoplantar pustulosis and psoriasis. We also discuss molecular studies aimed at understanding the role of tonsils in skin disease