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Oncogene Nov 2021Collagens are the most abundant proteins in the body and comprise the basement membranes and stroma through which cancerous invasion occurs; however, a pro-neoplastic...
Collagens are the most abundant proteins in the body and comprise the basement membranes and stroma through which cancerous invasion occurs; however, a pro-neoplastic function for mutant collagens is undefined. Here we identify COL11A1 mutations in 66 of 100 cutaneous squamous cell carcinomas (cSCCs), the second most common U.S. cancer, concentrated in a triple helical region known to produce trans-dominant collagens. Analysis of COL11A1 and other collagen genes found that they are mutated across common epithelial malignancies. Knockout of mutant COL11A1 impairs cSCC tumorigenesis in vivo. Compared to otherwise genetically identical COL11A1 wild-type tissue, gene-edited mutant COL11A1 skin is characterized by induction of β1 integrin targets and accelerated neoplastic invasion. In mosaic tissue, mutant COL11A1 cells enhanced invasion by neighboring wild-type cells. These results suggest that specific collagens are commonly mutated in cancer and that mutant collagens may accelerate this process.
Topics: Animals; Carcinoma, Squamous Cell; Case-Control Studies; Collagen Type XI; Female; Humans; Integrin beta1; Mice; Mutation; Neoplasm Invasiveness; Neoplasm Transplantation; Protein Structure, Secondary; Skin Neoplasms; Exome Sequencing
PubMed: 34584216
DOI: 10.1038/s41388-021-02013-y -
Anais Brasileiros de Dermatologia 2023Human Polyomaviruses such as MCPyV and HPyV6 are frequently found as part of healthy skin microbiota and have been associated with Merkel cell carcinoma (MCC), pruritic... (Comparative Study)
Comparative Study
BACKGROUND
Human Polyomaviruses such as MCPyV and HPyV6 are frequently found as part of healthy skin microbiota and have been associated with Merkel cell carcinoma (MCC), pruritic and dyskeratotic dermatoses, respectively. Their presence in other types of skin conditions varies greatly depending on lesion type and population.
OBJECTIVE
To analyse comparatively the presence of MCPyV and HPyV6 in nonmelanoma skin cancers and healthy skin.
METHODS
The authors utilized qPCR techniques to quantify these pathogens in NMSC, premalignant diseases, and healthy skin of 87 patients.
RESULTS
MCPyV was detected in over 40% of samples, while HPyV6 was in 9.6%. MCPyV load was higher in squamous cell carcinomas (SCC) compared to basal cell carcinomas (BCC) (p=0.016) and HPyV6 showed a higher percentage of infected cells in areas of low solar exposure as well as normal skin (p=0.012). A fair agreement (kappa=0.301) was found between MCPyV detection in lesions and their respective perilesional skin, indicating a random process of local dissemination of the virus.
STUDY LIMITATIONS
The lack of a larger sampling of different lesion types and protein expression analyses limits the correlation findings.
CONCLUSION
This is the first report of HPyV6 detection in the healthy skin of a Brazilian population, but the role of both polyomaviruses in NMSC has yet to be demonstrated.
Topics: Humans; Carcinoma, Basal Cell; Carcinoma, Merkel Cell; DNA, Viral; Merkel cell polyomavirus; Polyomavirus; Skin Neoplasms
PubMed: 36635157
DOI: 10.1016/j.abd.2022.02.006 -
Journal of Feline Medicine and Surgery Apr 2022This study aimed to understand epidemiological factors associated with feline cystadenomatosis, including signalment and papillomavirus PCR status. Cystadenomatosis is...
OBJECTIVES
This study aimed to understand epidemiological factors associated with feline cystadenomatosis, including signalment and papillomavirus PCR status. Cystadenomatosis is an uncommon condition primarily involving the ceruminous and apocrine skin and ear glands.
METHODS
This was a retrospective case series. Clinical records from 2011 to 2019 from a tertiary referral hospital in Boston, MA, USA were screened for cases, and case data were re-evaluated and analyzed. The total patient pool contained 65,385 individual cats, of which 797 were referred to the dermatology service. Medical records and biopsy specimens were reviewed; the information collected included signalment, clinical signs, physical examination and diagnostic tests, comorbidities and histopathologic findings. PCR was performed on biopsy specimens to test for papillomavirus DNA.
RESULTS
The cystadenomatosis population consisted of 57 cases (7.1% of total cases referred to the dermatology service) with 105 affected ears. Twenty-seven cases (48 ears) were confirmed via histopathology; four cats (7%) exhibited clinically cystic lesions on the periocular, periorbital and perianal regions; only one cat did not have pinnal lesions. Domestic shorthair cats were most often affected. Relative risk for cystadenomatosis was 2.24 times higher in male cats. In 48 cats (84.2%), ears were bilaterally affected. Seven cats (12.3%) had malignant neoplasia, which included: inflamed adenocarcinoma (n = 5); mast cell tumor (n = 1); or squamous cell carcinoma (n = 1). PCR testing on biopsy specimens from 24 cats revealed feline papillomavirus type 2 DNA in only four cats.
CONCLUSIONS AND RELEVANCE
Cystadenomatosis was more prevalent in senior non-purebred cats, over-represented in male cats and did not appear to be associated with papillomavirus, feline infectious peritonitis, feline immunodeficiency virus/feline leukemia virus status or other identifiable illnesses. Further studies are needed to investigate the causes of cystadenomatosis.
Topics: Animals; Cat Diseases; Cats; Feline Infectious Peritonitis; Immunodeficiency Virus, Feline; Leukemia Virus, Feline; Male; Papillomaviridae; Retrospective Studies; Skin
PubMed: 34254846
DOI: 10.1177/1098612X211024498 -
Proceedings of the National Academy of... Jan 2024Our understanding of how human skin cells differ according to anatomical site and tumour formation is limited. To address this, we have created a multiscale spatial...
Our understanding of how human skin cells differ according to anatomical site and tumour formation is limited. To address this, we have created a multiscale spatial atlas of healthy skin and basal cell carcinoma (BCC), incorporating in vivo optical coherence tomography, single-cell RNA sequencing, spatial global transcriptional profiling, and in situ sequencing. Computational spatial deconvolution and projection revealed the localisation of distinct cell populations to specific tissue contexts. Although cell populations were conserved between healthy anatomical sites and in BCC, mesenchymal cell populations including fibroblasts and pericytes retained signatures of developmental origin. Spatial profiling and in silico lineage tracing support a hair follicle origin for BCC and demonstrate that cancer-associated fibroblasts are an expansion of a + subpopulation associated with hair follicles in healthy skin. pericytes are also expanded in BCC suggesting a role in vascular remodelling. We propose that the identity of mesenchymal cell populations is regulated by signals emanating from adjacent structures and that these signals are repurposed to promote the expansion of skin cancer stroma. The resource we have created is publicly available in an interactive format for the research community.
Topics: Humans; Carcinoma, Basal Cell; Skin Neoplasms; Skin; Hair Follicle
PubMed: 38165934
DOI: 10.1073/pnas.2313326120 -
Tissue & Cell Oct 2022Suprabasin is a newly discovered protein linked to various human diseases including cancer. It may does have an effect on the development and expression of some...
INTRODUCTION
Suprabasin is a newly discovered protein linked to various human diseases including cancer. It may does have an effect on the development and expression of some non-melanoma skin cancers such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC is the most common non-melanoma skin cancers worldwide, while SCC comes as the second in terms of prevalence. In certain cases, it is very important to distinguish between these two carcinomas from each other and from normal skin samples. This study was aimed at investigating the characteristics of suprabasin expression in squamous cell carcinoma and basal cell carcinoma and whether it can be used as a biomarker.
MATERIALS AND METHODS
Thirty control, ninety SCC and thirty BCC cases obtained from the archives of the Department of Pathology, Faculty of Medicine, Fırat University, were examined by immunohistochemical staining for suprabasin.
RESULTS
Increased suprabasin expression was observed in tumour tissues and normal skin samples in SCC. As the grade increased in SCC, suprabasin expression decreased. No suprabasin expression was observed in the lesion area in BCC.
CONCLUSION
Suprabasin can be reported as a biomarker for SCC and used to differentiate SCC from BCC. Expression of suprabasin in SCC can be used to determine grade. Absence of suprabasin expression in BCC can be used for differential diagnosis.
Topics: Biomarkers; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Skin Neoplasms
PubMed: 35930991
DOI: 10.1016/j.tice.2022.101875 -
The British Journal of Dermatology Dec 2019Genome-wide association studies (GWAS) have identified thousands of susceptibility variants, although most have been associated with small individual risk estimates that... (Review)
Review
BACKGROUND
Genome-wide association studies (GWAS) have identified thousands of susceptibility variants, although most have been associated with small individual risk estimates that offer little predictive value. However, combining multiple variants into polygenic risk scores (PRS) may be more informative. Multiple studies have developed PRS composed of GWAS-identified variants for cutaneous cancers. This review highlights data from these studies.
OBJECTIVES
To review published GWAS and PRS studies for melanoma, cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC), and discuss their potential clinical utility.
METHODS
We searched PubMed and the National Human Genome Research Institute-European Bioinformatics Institute GWAS catalogue to identify relevant studies.
RESULTS
Results from 21 GWAS (11 melanoma, 3 cSCC, 7 BCC) and 11 PRS studies are summarized. Six loci in pigmentation genes overlap between these three cancers (ASIP/RALY, IRF4, MC1R, OCA2, SLC45A2 and TYR). Additional loci overlap for cSCC/BCC and BCC/melanoma, but no other loci are shared between cSCC and melanoma. PRS for melanoma show roughly two-to-threefold increases in risk and modest improvements in risk prediction (2-7% increases). PRS are associated with twofold and threefold increases in risk of cSCC and BCC, respectively, with small improvements (2% increase) in predictive ability.
CONCLUSIONS
Existing data indicate that PRS may offer small, but potentially meaningful, improvements to risk prediction. Additional research is needed to clarify the potential utility of PRS in cutaneous carcinomas. Clinical translation will require well-powered validation studies incorporating known risk factors to evaluate PRS as tools for screening. What's already known about this topic? Over 50 susceptibility loci for melanoma, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) have been identified in genome-wide association studies (GWAS). Polygenic risk scores (PRS) using variants identified from GWAS have also been developed for melanoma, BCC and cSCC, and investigated with respect to clinical risk prediction. What does this study add? This review provides an overview of GWAS findings and the potential clinical utility of PRS for melanoma, BCC and cSCC.
Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Genetic Predisposition to Disease; Genetic Testing; Genome-Wide Association Study; Humans; Melanoma; Multifactorial Inheritance; Risk Assessment; Risk Factors; Skin Neoplasms
PubMed: 30908599
DOI: 10.1111/bjd.17917 -
Communications Biology Aug 2022The Frankfurt specimen of the early-branching ceratopsian dinosaur Psittacosaurus is remarkable for the exquisite preservation of squamous (scaly) skin and other soft... (Review)
Review
The Frankfurt specimen of the early-branching ceratopsian dinosaur Psittacosaurus is remarkable for the exquisite preservation of squamous (scaly) skin and other soft tissues that cover almost its entire body. New observations under Laser-Stimulated Fluorescence (LSF) reveal the complexity of the squamous skin of Psittacosaurus, including several unique features and details of newly detected and previously-described integumentary structures. Variations in the scaly skin are found to be strongly regionalized in Psittacosaurus. For example, feature scales consist of truncated cone-shaped scales on the shoulder, but form a longitudinal row of quadrangular scales on the tail. Re-examined through LSF, the cloaca of Psittacosaurus has a longitudinal opening, or vent; a condition that it shares only with crocodylians. This implies that the cloaca may have had crocodylian-like internal anatomy, including a single, ventrally-positioned copulatory organ. Combined with these new integumentary data, a comprehensive review of integument in ceratopsian dinosaurs reveals that scalation was generally conservative in ceratopsians and typically consisted of large subcircular-to-polygonal feature scales surrounded by a network of smaller non-overlapping polygonal basement scales. This study highlights the importance of combining exceptional specimens with modern imaging techniques, which are helping to redefine the perceived complexity of squamation in ceratopsians and other dinosaurs.
Topics: Animals; Carcinoma, Squamous Cell; Dinosaurs; Fossils; Preservation, Biological; Skin
PubMed: 35962036
DOI: 10.1038/s42003-022-03749-3 -
Acta Otorhinolaryngologica Italica :... Feb 2020
Review
Topics: Carcinoma, Basal Cell; Disease Management; Face; Head; Head and Neck Neoplasms; Humans; Otolaryngology; Risk Factors; Skin; Skin Neoplasms; Surgeons
PubMed: 31388193
DOI: 10.14639/0392-100X-2245 -
Acta Dermato-venereologica Jan 2021Basosquamous carcinoma is a rare clinical entity, which comprises 1.7-2.7% of all skin carcinomas. It is described as a basal cell carcinoma with features of squamous...
Basosquamous carcinoma is a rare clinical entity, which comprises 1.7-2.7% of all skin carcinomas. It is described as a basal cell carcinoma with features of squamous differentiation. To date, studies of the epidemiology of basosquamous carcinoma have been few and small in size. We report here the most extensive series of basosquamous carcinomas published to date, highlighting the differences between basosquamous carcinoma and other keratinizing tumours. Patients undergoing surgical excision for keratinizing tumours were enrolled in this study. Age, sex and tumour characteristics were recorded. A total of 1,519 squamous cell carcinomas, 288 basosquamous carcinomas and 4,235 basal cell carcinomas were collected. Basosquamous features were compared with those of basal cell and squamous cell carcinomas. For basosquamous carcinomas, 70.5% were located on the head and neck, particularly on the nose, forehead and cheeks, and represented almost 10% of the keratinizing tumours on the ears. Significant differences were found between basosquamous carcinoma and basal cell or squamous cell carcinomas. Basosquamous carcinoma should be considered a distinct type of keratinizing tumour with different anatomical, sex and age distributions.
Topics: Carcinoma, Basal Cell; Carcinoma, Basosquamous; Carcinoma, Squamous Cell; Cheek; Humans; Skin Neoplasms
PubMed: 33269406
DOI: 10.2340/00015555-3710 -
American Journal of Clinical Dermatology May 2022Actinic keratosis (AK) is a chronic skin disease in which clinical and subclinical cutaneous lesions coexist on sun-exposed areas such as the head and neck region and... (Review)
Review
Actinic keratosis (AK) is a chronic skin disease in which clinical and subclinical cutaneous lesions coexist on sun-exposed areas such as the head and neck region and the extremities. The high prevalence of AK means the disease burden is substantial, especially in middle-aged and elderly populations. Evidence indicates that AK may progress into invasive cutaneous squamous cell carcinoma, so the European guidelines recommend treatment of any AK regardless of clinical severity. Given the aging population and therefore the increasing incidence of AK and cutaneous field carcinogenesis, further updates on the long-term efficacy of current therapies and new investigational agents are critical to guide treatment choice. Patients often have difficulty adequately applying topical treatments and coping with adverse local skin reactions, leading to less than optimum treatment adherence. The development of associated local skin symptoms and cosmetic outcomes for the area of interest are also relevant to the choice of an appropriate therapeutic strategy. Treatment is always individually tailored according to the characteristics of both patients and lesions. This review focuses on the therapeutic approaches to AK and illustrates the currently available home-based and physician-managed treatments.
Topics: Administration, Topical; Aged; Carcinoma, Squamous Cell; Humans; Keratosis, Actinic; Middle Aged; Skin; Skin Neoplasms
PubMed: 35182332
DOI: 10.1007/s40257-022-00674-3