Somatic expression of LINE-1 elements in human tissues

LINE-1 expression damages host DNA via insertions and endonuclease-dependent DNA double-strand breaks (DSBs) that are highly toxic and mutagenic. The predominant tissue of LINE-1 expression has been considered to be the germ line. We show that both full-length and processed L1 transcripts are widespread in human somatic tissues and transformed cells, with significant variation in both L1 expression and L1 mRNA processing. This is the first demonstration that RNA processing is a major regulator of L1 activity. Many tissues also produce translatable spliced transcript (SpORF2). An Alu retrotransposition assay, COMET assays and 53BP1 foci staining show that the SpORF2 product can support functional ORF2 protein expression and can induce DNA damage in normal cells. Tests of the senescence-associated β-galactosidase expression suggest that expression of exogenous full-length L1, or the SpORF2 mRNA alone in human fibroblasts and adult stem cells triggers a senescence-like phenotype, which is one of the reported responses to DNA damage. In contrast to previous assumptions that L1 expression is germ line specific, the increased spectrum of tissues exposed to L1-associated damage suggests a role for L1 as an endogenous mutagen in somatic tissues. These findings have potential consequences for the whole organism in the form of cancer and mammalian aging

The incidence of skin cancer in dermatology

Background It is known that the incidence of skin cancer is rising rapidly worldwide, but no reliable figures on multiple nonmelanoma skin cancer (NMSC) are available. Aim To determine the actual incidence of skin cancer in dermatology practice and to estimate how this relates to the first primary tumours (registered at the Eindhoven Cancer Registry). Methods We examined 1001 randomly selected patient records at Catharina Hospital Eindhoven for mention of skin cancer. For each patient, skin cancers were recorded in a database, starting from 1 January 2004 until 1 March 2010. The time interval between tumours and any history of skin cancer were also recorded. Results Of this group, 876 patients were treated for skin cancer during the study period. We recorded a total of 2106 tumours with a mean of 2.4 skin cancers per patient. Nearly half (46%) of patients developed multiple tumours, and the second tumour developed within a median period of 5 months. Over a quarter (28%) of patients were known to have had skin cancer before 2004, the start of the study period. Conclusions The number of NMSCs in practice differs substantially from the number of first primary histologically confirmed NMSCs, as usually reported by the Eindhoven Cancer Registry. To obtain the optimum benefit from registration of NMSC, it is recommended to register all NMSCs, because only this complete number will give an insight into the incidence of the rising skin-cancer numbers. Because subsequent tumours occur frequently, NMSC should be regarded as a chronic disease, and innovations in disease management are required for cost-effective control. Click here for the corresponding questions to this CME article. © 2013 British Association of Dermatologists

Congenital naevi treated with erbium: YAG laser (Derma K) resurfacing in neonates: clinical results and review of the literature

Background Giant congenital melanocytic naevi (CMN) are often disfiguring, potentially malignant pigmented lesions present at birth. Their management is based on two main considerations: attempt to minimize the risk of malignancy and to obtain an acceptable cosmetic result. In the past various approaches have been used to treat these naevi. Objectives To describe clinical and histopathological results after treatment of CMN in neonates with erbium:YAG (Er:YAG) laser resurfacing. Methods Ten children with CMN were treated with Er:YAG laser resurfacing in the first weeks of life. Results Laser ablation was well tolerated by all children and immediate results were good. At a total follow-up ranging from 3 to 36 months we saw good results, with no or minimal repigmentation, in eight of 10 patients. Patients experienced minimal side-effects such as postoperative pain, bleeding and scar formation. Postoperative histopathology showed disappearance of heavily pigmented cells in the upper part of the dermis. Conclusions Er:YAG laser resurfacing is an effective method of ablating CMN, with minimal scarring and postoperative complications