Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma

Squamous cell carcinomas (SCCs) are one of the most frequent forms of human malignancy, but, other than TP53 mutations, few causative somatic aberrations have been identified. We identified NOTCH1 or NOTCH2 mutations in ~75% of cutaneous SCCs and in a lesser fraction of lung SCCs, defining a spectrum for the most prevalent tumor suppressor specific to these epithelial malignancies. Notch receptors normally transduce signals in response to ligands on neighboring cells, regulating metazoan lineage selection and developmental patterning. Our findings therefore illustrate a central role for disruption of microenvironmental communication in cancer progression. NOTCH aberrations include frameshift and nonsense mutations leading to receptor truncations as well as point substitutions in key functional domains that abrogate signaling in cell-based assays. Oncogenic gain-of-function mutations in NOTCH1 commonly occur in human T-cell lymphoblastic leukemia/lymphoma and B-cell chronic lymphocytic leukemia. The bifunctional role of Notch in human cancer thus emphasizes the context dependency of signaling outcomes and suggests that targeted inhibition of the Notch pathway may induce squamous epithelial malignancies.     

Factors affecting sunscreen use and sun avoidance in a U.S. national sample of organ transplant recipients

Background Organ transplant recipients have an increased risk of nonmelanoma skin cancers due to immunosuppressive therapy following transplantation. Use of sunscreen has been shown to reduce this risk. Objectives To identify patient and healthcare factors associated with sun‐protective behaviours in organ transplant recipients after transplantation with the goal of increasing overall sunscreen use. Methods This study utilized a cross‐sectional, retrospective survey from a national sample of 198 organ transplant recipients in the U.S.A. from 2004 to 2008 with no prior diagnosis of skin cancer. The main outcome measures were sunscreen use and sun avoidance before and after transplantation. Frequency of sunscreen use and sun exposure was obtained by self‐report on Likert scales ranging from never to always, and these responses were converted to a numerical scale from 0 to 4. Results Overall sunscreen use increased after transplantation (from a score of 1·4 to 2·1, P < 0·001). Sex, Fitzpatrick skin type, receiving advice to avoid sun from a healthcare provider, and pretransplantation sunscreen use were significantly associated with frequency of post‐transplantation sunscreen use in multivariate models. Pretransplantation sun exposure, advice to avoid sun and pretransplantation sunscreen use were significantly associated with sun avoidance post‐transplantation. Conclusions Both patient features and clinician advice are associated with sun‐protective behaviours after organ transplantation. These results will help physicians target expanded sun‐protection counselling to those patients most in need of such intervention.     

Self-injurious behaviour in Cornelia de Lange syndrome: 1. Prevalence and phenomenology

Background   Self-injurious behaviour is frequently identified as part of the behavioural phenotype of Cornelia de Lange syndrome (CdLS). We conducted a case-control study of the prevalence and phenomenology of self-injurious behaviour (SIB) in CdLS.
Methods   A total of 54 participants with CdLS were compared with 46 individuals who were comparable on key variables including age, degree of intellectual disability and wheelchair use, using questionnaire and observational measures.
Results   Clinically significant self-injury was not more prevalent in the CdLS group (55.6%), nor was it different in presentation from that seen in the comparison group. Hyperactivity, stereotyped and compulsive behaviours predicted clinically significant self-injury in all participants. Hand directed, mild self-injury was more prevalent in CdLS.
Conclusions   The results show that clinically significant self-injury may not be part of the behavioural phenotype of CdLS but a specific body target for proto-SIB is more common.