Differential gene hypermethylation in genital lichen sclerosus and cancer: a comparative study

Guerrero-Setas, David; Pérez-Janices, Noemí; Ojer, Amaya; Blanco‐Fernández, Laura; Guarch-Troyas, Carmen; Guarch, Rosa

doi:10.1111/his.12204

Cited by 22 publications

(24 citation statements)

References 74 publications

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“…The primers used in these experiments (Sigma, St. Louis, MI, USA) are described in detail in http://onlinelibrary.wiley.com/doi/10.1111/pin.12332/suppinfo. The annealing temperatures were reported previously . Positive and negative controls were included in each bisulfite treatment and MSP to confirm the presence or absence of the band of expected size for each control, respectively.…”

Section: Methodssupporting

confidence: 86%

“…In this report, the hypermethylation of genes involved in key cellular regulatory pathways ( EPB41L3, P16 , RASSF1A , RASSF2 , TSLC‐1 and TSP‐1 genes) was analyzed in tumors (SCC, ADC) and precursor lesions (cervical intraepithelial lesions, CIN) of the uterine cervix. The hypermethylation of some of these genes and their clinical role were firstly described in other types of cancer by our group …”

mentioning

confidence: 84%

“…The annealing temperatures were reported previously. [8][9][10] Positive and negative controls were included in each bisulfite treatment and MSP to confirm the presence or absence of the band of expected size for each control, respectively. DNA from lymphocytes treated in vitro with SssI methylase (New England Biolabs, Ipswich, MA, USA) was used as a positive control for methylated alleles.…”

Section: Methylation-specific Pcr (Msp)mentioning

confidence: 99%

“…The hypermethylation of some of these genes Correspondence: David Guerrero-Setas, PhD, MSc, Navarrabiomed-Fundación Miguel Servet, Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, 3 Irunlarrea street, and their clinical role were firstly described in other types of cancer by our group. [7][8][9][10][11] EPB41L3 belongs to the membrane-associated cytoskeleton protein 4.1 family. 12 This protein was previously found to be downregulated or lost in more than half of primary nonsmall cell lung cancers (NSCLC) and prostate cancer.…”

mentioning

confidence: 99%

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Differential role of gene hypermethylation in adenocarcinomas, squamous cell carcinomas and cervical intraepithelial lesions of the uterine cervix

Blanco‐Luquin

Guarch

Ojer

et al. 2015

Pathology International

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Cervical cancer is the third most common cancer in women worldwide. The hypermethylation of P16, TSLC-1 and TSP-1 genes was analyzed in squamous cell carcinomas (SCC), cervical intraepithelial lesions (CIN) and adenocarcinomas (ADC) of the uterine cervix (total 181 lesions). Additionally human papillomavirus (HPV) type, EPB41L3, RASSF1 and RASSF2 hypermethylation were tested in ADC and the results were compared with those obtained previously by our group in SCC. P16, TSLC-1 and TSP-1 hypermethylation was more frequent in SCCs than in CINs. These percentages and the corresponding ones for EPB41L3, RASSF1 and RASSF2 genes were also higher in SCCs than in ADCs, except for P16. The presence of HPV in ADCs was lower than reported previously in SCC and CIN. Patients with RASSF1A hypermethylation showed significantly longer disease-free survival (P = 0.015) and overall survival periods (P = 0.009) in ADC patients. To our knowledge, this is the first description of the EPB41L3 and RASSF2 hypermethylation in ADCs. These results suggest that the involvement of DNA hypermethylation in cervical cancer varies depending on the histological type, which might contribute to explaining the different prognosis of patients with these types of tumors.

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Section: Methodssupporting

confidence: 86%

mentioning

confidence: 84%

Section: Methylation-specific Pcr (Msp)mentioning

confidence: 99%

mentioning

confidence: 99%

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Differential role of gene hypermethylation in adenocarcinomas, squamous cell carcinomas and cervical intraepithelial lesions of the uterine cervix

Blanco‐Luquin

Guarch

Ojer

et al. 2015

Pathology International

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“…Other genes that have been found to be hypermethylated in genital lichen sclerosus and cancer include RASSF1, TSLC1, and TSP1 44. More recently, in a cohort of 60 patients compared with 20 normal controls, the promoter of the tumor suppressor gene IRF6 was shown to be hypermethylated in 9 (45%) of 20 lichen sclerosus adjacent to vulvar squamous carcinoma specimens, 16 (80%) of 20 vulvar squamous carcinoma specimens, 2 (10%) of 20 cancer-free lichen sclerosus specimens, and 0 of 20 normal skin specimens 45…”

Section: Methodsmentioning

confidence: 99%

Clinical and molecular classification of vulvar squamous pre-cancers

Cohen

Anderson

Eva

et al. 2019

Int J Gynecol Cancer

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Vulvar intraepithelial neoplasia (VIN) is a precursor to vulvar squamous cell carcinoma and is defined histopathologically by the presence of atypia. VIN has been classified into two types: usual vulvar intraepithelial neoplasia (uVIN), which is also referred to as a vulvar high-grade squamous intra-epithelial lesion (HSIL), and differentiated VIN (dVIN). The former is associated with chronic infection by sub-types of the human papilloma virus (HPV), whereas dVIN is HPV-independent and frequently associated with lichen sclerosus. The distinction is important because dVIN has a greater risk of, and more rapid transit to, vulvar squamous cell carcinoma. Furthermore, dVIN-associated vulvar cancers have an increased risk of recurrence and higher mortality than those arising from HSIL. Molecular characterization of vulvar squamous cell carcinoma precursors using next-generation sequencing is a relatively novel, but rapidly advancing field. This review appraises recent studies that have investigated the risks of progression to vulvar malignancy associated with HSIL and dVIN, the prognosis of HPV-dependent and HPV-independent vulvar squamous cell carcinomas, and conducted next generation sequencing mutation analyses to elucidate the genomic profiles underlying VIN. These studies suggest that HSIL and dVIN are characterized by different underlying molecular alterations that may have important implications for treatment and follow-up of women diagnosed with vulvar squamous cell cancer.

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Dermatoses of the Male Genitalia

Bunker,

Watchorn

2024

Rook's Textbook of Dermatology

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Male genital dermatoses present a diverse array of symptoms including itch, pain, cracking, blistering, bruising, dysuria and dyspareunia, and can affect quality of life in terms of sexual, dermatological, psychological and urological morbidity. Dermatoses such as psoriasis, lichen planus and atopic eczema may manifest in specific morphology in the genital region, while other dermatoses such as lichen sclerosus, have a genital predilection, and subtle clinical signs that require assiduous assessment and a trained eye to detect. Treatment may present similar challenges due to the essential functions and associated stressors in the region. Precancerous pathologies also present challenges in terms of clinical recognition, and treatment, with diverse morphologies and region‐specific predisposing factors, and surgical challenges in terms of preserving sexual and urinary function.

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Differential gene hypermethylation in genital lichen sclerosus and cancer: a comparative study

Cited by 22 publications

References 74 publications

Differential role of gene hypermethylation in adenocarcinomas, squamous cell carcinomas and cervical intraepithelial lesions of the uterine cervix

Differential role of gene hypermethylation in adenocarcinomas, squamous cell carcinomas and cervical intraepithelial lesions of the uterine cervix

Clinical and molecular classification of vulvar squamous pre-cancers

Dermatoses of the Male Genitalia

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