S1-Guideline Cutaneous Angiosarcomas - Update 2021

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Association of toll-interacting protein gene polymorphisms with atopic dermatitis

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disorder, affecting up to 15% of children in industrialized countries. Toll-interacting protein (TOLLIP) is an inhibitory adaptor protein within the toll-like receptor (TLR) pathway, a part of the innate immune system that recognizes structurally conserved molecular patterns of microbial pathogens, leading to an inflammatory immune response. METHODS: In order to detect a possible role of TOLLIP variation in the pathogenesis of AD, we screened the entire coding sequence of the TOLLIP gene by SSCP in 50 AD patients. We identified an amino acid exchange in exon 6 (Ala222Ser) and a synonymous variation in exon 4 (Pro139Pro). Subsequently, these two variations and four additional non-coding polymorphisms (-526 C/G, two polymorphisms in intron 1 and one in the 3'UTR) were genotyped in 317 AD patients and 224 healthy controls. RESULTS: The -526G allele showed borderline association with AD in our cohort (p = 0.012; significance level after correction for multiple testing 0.0102). Haplotype analysis did not yield additional information. Evaluation of mRNA expression by quantitative real-time polymerase chain reaction in six probands with the CC and six with the GG genotype at the -526 C/G locus did not reveal significant differences between genotypes. CONCLUSION: Variation in the TOLLIP gene may play a role in the pathogenesis of AD. Yet, replication studies in other cohorts and populations are warranted to confirm these association results

Zur Genetik der Atopischen Dermatitis

Die Atopische Dermatitis (Neurodermitis) ist ein häufiges dermatologisches Krankheitsbild multifaktorieller Genese. In dieser Arbeit wurden Polymorphismen in zwei Kandidatengenen des angeborenen Immunsystems auf eine mögliche Assoziation zur Atopischen Dermatitis untersucht. $\textit {Toll interacting protein (TOLLIP)}$ und $\textit {TIR-domain containing adaptor protein (TIRAP)}$ wurden mit der $\textit {single strand conformation polymorphism}$ (SSCP)-Methode gescreent. Gefundene Polymophismen wurden anschließend mit der it restriction fragment lengh polymorphism (RFLP)-Methode an einem Patientenkollektiv (n=317) und an gesunden Kontrollen (n=224) typisiert. Im $\it TOLLIP$-Gen fand sich ein Promotorpolymorphismus mit signifikanter Assoziation zur Atopischen Dermatitis. Variationen in Genen des angeborenen Immunsystems könnten somit eine wichtige Rolle in der Pathogene der Atopischen Dermatitis spielen

Structure, Biosynthesis, and Occurrence of Bacterial Pyrrolizidine Alkaloids

Pyrrolizidine alkaloids (PAs) are widespread plant natural products with potent toxicity and bioactivity. Herein, the identification of bacterial PAs from entomopathogenic bacteria using differential analysis by 2D NMR spectroscopy (DANS) and mass spectrometry is described. Their biosynthesis was elucidated to involve a non-ribosomal peptide synthetase. The occurrence of these biosynthesis gene clusters in Gram-negative and Gram-positive bacteria indicates an important biological function in bacteria

Localization of PD‐L1 on single cancer cells by iSERS microscopy with Au/Au core/satellite nanoparticles

Programmed cell death‐ligand 1 (PD‐L1) is an important predictive biomarker. The detection of PD‐L1 can be crucial for patients with advanced cancer where the use of immunotherapy is considered. Here, we demonstrate the use of immuno‐SERS microscopy (iSERS) for localizing PD‐L1 on single cancer SkBr‐3 cells. A central advantage of iSERS is that the disturbing autofluorescence from cells and tissues can be efficiently minimized by red to near‐infrared laser excitation. In this study we employed Au/Au core/satellite nanoparticles as SERS nanotags because of their remarkable signal brightness and colloidal stability upon red laser excitation. False‐color iSERS images of the positive and negative controls clearly reveal the specific localization of PD‐L1 with SERS nanotag‐labeled antibodies

TERT promoter mutations are frequent in cutaneous basal cell carcinoma and squamous cell carcinoma.

Activating mutations in the TERT promoter were recently identified in up to 71% of cutaneous melanoma. Subsequent studies found TERT promoter mutations in a wide array of other major human cancers. TERT promoter mutations lead to increased expression of telomerase, which maintains telomere length and genomic stability, thereby allowing cancer cells to continuously divide, avoiding senescence or apoptosis. TERT promoter mutations in cutaneous melanoma often show UV-signatures. Non-melanoma skin cancer, including basal cell carcinoma and squamous cell carcinoma, are very frequent malignancies in individuals of European descent. We investigated the presence of TERT promoter mutations in 32 basal cell carcinomas and 34 cutaneous squamous cell carcinomas using conventional Sanger sequencing. TERT promoter mutations were identified in 18 (56%) basal cell carcinomas and in 17 (50%) cutaneous squamous cell carcinomas. The recurrent mutations identified in our cohort were identical to those previously described in cutaneous melanoma, and showed a UV-signature (C>T or CC>TT) in line with a causative role for UV exposure in these common cutaneous malignancies. Our study shows that TERT promoter mutations with UV-signatures are frequent in non-melanoma skin cancer, being present in around 50% of basal and squamous cell carcinomas and suggests that increased expression of telomerase plays an important role in the pathogenesis of these tumors

S1-Guideline Cutaneous Angiosarcomas - Update 2021

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