Identification of human papillomavirus DNA in cutaneous lesions of Cowden syndrome

Background: Cowden syndrome (CS) or multiple hamartoma syndrome is a cancer-associated genodermatosis inherited in an autosomal dominant pattern. One of the diagnostic criteria is facial papules which are felt to be trichilemmomas, benign hair follicle tumors, which some consider to be induced by human papillomavirus (HPV). Objective: To search for HPV in skin tumors, especially trichilemmomas, from patients with CS. Methods: Skin lesions from patients with CS were classified histologically. Each tumor was then analyzed for HPV DNA by polymerase chain reaction with different primer sets; positive amplicons were typed by direct sequencing. Results: Twenty-nine biopsies from 7 patients with CS were investigated. Only 2 of 29 tumors clinically suspected of being trichilemmomas were confirmed histologically. In addition, 3 sclerotic fibromas, also typical of CS, were found, as well as 1 sebaceous hyperplasia. The other 23 lesions showed histological features of HPV-induced tumors in various stages of development. HPV DNA was found in 19 of 29 cutaneous lesions. Tumors without any histological signs of HPV induction were negative for HPV DNA. Two tumors which were histologically classified as common warts contained HPV types 27 and 28. All the 17 other HPV types belong to the group of epidermodysplasia-verruciformis-associated types. Conclusions: The majority of cutaneous lesions in CS contain HPV DNA. They may have a variety of histological patterns. Trichilemmomas are not clinically distinctive and can be difficult to identify in CS patients. Copyright (C) 2003 S. Karger AG, Basel

MicroRNA expression differs in cutaneous squamous cell carcinomas and healthy skin of immunocompetent individuals

Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers, but the influence of microRNA (miRNA) expression has only been sporadically analysed. We hypothesized that miRNAs are differentially expressed in cSCC and hence influence its development. We therefore isolated total miRNA from well-differentiated cSCCs and from controls without SCC. Expression analyses of 12 miRNAs showed three significantly differentially expressed miRNAs. We identified a significant upregulation of the miR-21 and the miR-31, a proto-oncogene like miR-21. While the upregulated expression of miR-21 has been known for some time, the increased expression of miR-31 was never shown so clearly. Furthermore, we showed the upregulation of miRNA-205, which has never been described before. The miR-205 induces specific keratinocyte migration and could be a characteristic marker for cSCC. It has to be determined in following studies whether these upregulated expressions are specific for cSCC and if so, for which cSCC stages

The phenotypic and genotypic spectra of ichthyosis with confetti plus novel genetic variation in the 3' end of KRT10: from disease to a syndrome

Ichthyosis with confetti (IWC) is a genodermatosis caused by dominant negative mutations in the gene encoding keratin 10 (KRT10). We investigated clinical and genetic details of a substantial number of patients with IWC in order to define major and minor criteria for diagnosis of this rare disorder.; Parallel clinical investigation of 6 patients with IWC revealed a novel spectrum of phenotypes. We found several features that qualify as major criteria for diagnosis, which are clearly and consistently associated with the condition. These included malformation of ears, hypoplasia of mammillae, and dorsal acral hypertrichosis. Genetic analysis of patients revealed several different frameshift mutations in intron 6 or exon 7 of KRT10. Analysis of this locus in 17 unrelated control individuals revealed 2 novel polymorphisms of KRT10.; We present for the first time to our knowledge the spectrum of clinical variability of IWC in 6 patients with confirmed mutations in KRT10. From this, we have extracted major and minor criteria to aid early and correct clinical diagnosis. Ectodermal malformations, present in all patients, suggest a novel classification of IWC as a syndrome. There is remarkable genetic variation at the IWC disease locus within control individuals from the general population

Risk of Cutaneous Squamous Cell Carcinoma Development in Renal Transplant Recipients Is Independent of TMC/EVER Alterations

Renal transplant recipients (RTRs) have an increased risk of developing nonmelanoma skin cancer, mainly cutaneous squamous cell carcinoma (cSCC). Two genes (TMC6/EVER1 and TMC8/EVER2), mutated in epidermodysplasia verruciformis (EV) patients with an increased risk of cSCC development, contain numerous single-nucleotide polymorphisms (SNPs).; To evaluate the effect of SNPs in both TMC/EVER genes on the different susceptibilities of RTRs to cSCC.; We determined the occurrence of cSCC in 105 RTRs who were transplanted at least 7 years previously and investigated the frequency of 26 SNPs within both TMC/EVER genes in severely affected (n = 16) as well as in nonaffected RTRs (n = 25).; Our data did not indicate a significant association between any SNP genotype and risk of cSCC development in RTRs.; To clarify the correlation between SNPs in both TMC genes and cSCC development in RTRs, integrated investigations of large cohorts including both RTRs and immunocompetent individuals with consideration of cSCC status, SNP genotype and human papillomavirus status might be necessary

Risk of Cutaneous Squamous Cell Carcinoma Development in Renal Transplant Recipients Is Independent of TMC/EVER Alterations

Renal transplant recipients (RTRs) have an increased risk of developing nonmelanoma skin cancer, mainly cutaneous squamous cell carcinoma (cSCC). Two genes (TMC6/EVER1 and TMC8/EVER2), mutated in epidermodysplasia verruciformis (EV) patients with an increased risk of cSCC development, contain numerous single-nucleotide polymorphisms (SNPs).; To evaluate the effect of SNPs in both TMC/EVER genes on the different susceptibilities of RTRs to cSCC.; We determined the occurrence of cSCC in 105 RTRs who were transplanted at least 7 years previously and investigated the frequency of 26 SNPs within both TMC/EVER genes in severely affected (n = 16) as well as in nonaffected RTRs (n = 25).; Our data did not indicate a significant association between any SNP genotype and risk of cSCC development in RTRs.; To clarify the correlation between SNPs in both TMC genes and cSCC development in RTRs, integrated investigations of large cohorts including both RTRs and immunocompetent individuals with consideration of cSCC status, SNP genotype and human papillomavirus status might be necessary

Beyond Einstein-Cartan gravity: Quadratic torsion and curvature invariants with even and odd parity including all boundary terms

Recently, gravitational gauge theories with torsion have been discussed by an increasing number of authors from a classical as well as from a quantum field theoretical point of view. The Einstein-Cartan(-Sciama-Kibble) Lagrangian has been enriched by the parity odd pseudoscalar curvature (Hojman, Mukku, and Sayed) and by torsion square and curvature square pieces, likewise of even and odd parity. (i) We show that the inverse of the so-called Barbero-Immirzi parameter multiplying the pseudoscalar curvature, because of the topological Nieh-Yan form, can only be appropriately discussed if torsion square pieces are included. (ii) The quadratic gauge Lagrangian with both parities, proposed by Obukhov et al. and Baekler et al., emerges also in the framework of Diakonov et al.(2011). We establish the exact relations between both approaches by applying the topological Euler and Pontryagin forms in a Riemann-Cartan space expressed for the first time in terms of irreducible pieces of the curvature tensor. (iii) Only in a Riemann-Cartan spacetime, that is, in a spacetime with torsion, parity violating terms can be brought into the gravitational Lagrangian in a straightforward and natural way. Accordingly, Riemann-Cartan spacetime is a natural habitat for chiral fermionic matter fields.Comment: 12 page latex, as version 2 an old file was submitted by mistake, this is now the real corrected fil

Arginine- but not alanine-rich carboxy-termini trigger nuclear translocation of mutant keratin 10 in ichthyosis with confetti

Ichthyosis with confetti (IWC) is a genodermatosis associated with dominant-negative variants in keratin 10 (KRT10) or keratin 1 (KRT1). These frameshift variants result in extended aberrant proteins, localized to the nucleus rather than the cytoplasm. This mislocalization is thought to occur as a result of the altered carboxy (C)-terminus, from poly-glycine to either a poly-arginine or -alanine tail. Previous studies on the type of C-terminus and subcellular localization of the respective mutant protein are divergent. In order to fully elucidate the pathomechanism of IWC, a greater understanding is critical. This study aimed to establish the consequences for localization and intermediate filament formation of altered keratin 10 (K10) C-termini. To achieve this, plasmids expressing distinct KRT10 variants were generated. Sequences encoded all possible reading frames of the K10 C-terminus as well as a nonsense variant. A keratinocyte line was transfected with these plasmids. Additionally, gene editing was utilized to introduce frameshift variants in exon 6 and exon 7 at the endogenous KRT10 locus. Cellular localization of aberrant K10 was observed via immunofluorescence using various antibodies. In each setting, immunofluorescence analysis demonstrated aberrant nuclear localization of K10 featuring an arginine-rich C-terminus. However, this was not observed with K10 featuring an alanine-rich C-terminus. Instead, the protein displayed cytoplasmic localization, consistent with wild-type and truncated forms of K10. This study demonstrates that, of the various 3' frameshift variants of KRT10, exclusively arginine-rich C-termini lead to nuclear localization of K10

Classical Dynamics of the Time-Dependent Elliptical Billiard

In this work we study the nonlinear dynamics of the static and the driven ellipse. In the static case, we find numerically an asymptotical algebraic decay for the escape of an ensemble of non-interacting particles through a small hole due to the integrable structure of the phase space of the system. Furthermore, for a certain hole position a saturation value in the decay that can be tuned arbitrarily by varying the eccentricity of the ellipse is observed and explained. When applying harmonic boundary oscillations this saturation value caused by librator type orbits is gradually destroyed via two fundamental processes which are discussed in detail. As a result, an amplitude dependent emission rate is obtained in the long time behavior of the decay, suggesting that the driven elliptical billiard can be used as a controllable source of particles