Hypermethylation-Induced Inactivation of the<i>IRF6</i>Gene as a Possible Early Event in Progression of Vulvar Squamous Cell Carcinoma Associated With Lichen Sclerosus

Rotondo, John Charles; Borghi, Alessandro; Selvatici, Rita; Magri, Eros; Bianchini, E; Montinari, Elena; Corazza, Monica; Virgili, Annarosa; Tognon, Mauro; Martini, Fernanda

doi:10.1001/jamadermatol.2016.1336

Cited by 49 publications

(40 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both VIN and VSCC displayed several focal alterations of well‐known cancer‐related genes, including TP63 , CD44 , cyclin D1, and BCL2 . Altered CD44 protein and TP63 mRNA expression in vulvar lesions has been reported by others . Cyclin D1 amplifications were strongly associated with HPV‐negative lesions, whereas BCL2 and TP63 were more frequently affected in HPV‐positive cases.…”

Section: Discussionsupporting

confidence: 67%

Molecular heterogeneity in human papillomavirus‐dependent and ‐independent vulvar carcinogenesis

et al. 2018

View full text Add to dashboard Cite

Vulvar squamous cell carcinoma (VSCC) and precancerous vulvar intraepithelial neoplasia (VIN) can develop through human papillomavirus (HPV)‐dependent and ‐independent pathways, indicating a heterogeneous disease. Only a minority of VIN progress, but current clinicopathological classifications are insufficient to predict the cancer risk. Here we analyzed copy number alterations (CNA) to assess the molecular heterogeneity of vulvar lesions in relation to HPV and cancer risk. HPV‐status and CNA by means of whole‐genome next‐generation shallow‐sequencing were assessed in VSCC and VIN. The latter included VIN of women with associated VSCC (VINVSCC) and women who did not develop VSCC during follow‐up (VIN no VSCC). HPV‐testing resulted in 41 HPV‐positive (16 VINVSCC, 14 VIN no VSCC, and 11 VSCC) and 24 HPV‐negative (11 VINVSCC and 13 VSCC) lesions. HPV‐positive and ‐negative VSCC showed a partially overlapping pattern of recurrent CNA, including frequent gains of 3q and 8q. In contrast, amplification of 11q13/cyclinD1 was exclusively found in HPV‐negative lesions. HPV‐negative VINVSCC had less CNA than HPV‐negative VSCC (P = .009), but shared chromosome 8 alterations. HPV‐positive VIN no VSCC had less CNA than VINVSCC (P = .022). Interestingly, 1pq gain was detected in 81% of HPV‐positive VINVSCC and only in 21% of VIN no VSCC (P = .001). In conclusion, HPV‐dependent and ‐independent vulvar carcinogenesis is characterized by distinct CNA patterns at the VIN stage, while more comparable patterns are present at the cancer stage. Cancer risk in VIN seems to be reflected by the extent of CNA, in particular chromosome 1 gain in HPV‐positive cases.

show abstract

Section: Discussionsupporting

confidence: 67%

Molecular heterogeneity in human papillomavirus‐dependent and ‐independent vulvar carcinogenesis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…At the same time IRF6 is able to restrain DNp63 protein levels by enhancing its protein degradation (Moretti et al, 2010). Diverse genetic events such as promoter methylation and gene mutation impair IRF6 activity in SCC (Rotondo et al, 2016). Mutations of the IRF6 gene have been reported in 7% of HNSCC patients and down-regulation of IRF6 has been correlated with tumour invasive and differentiation status of SCC (Stransky et al, 2011).…”

Section: Genetic Determinants Of Dnp63 Oncogenic Activity In Sccmentioning

confidence: 99%

ΔNp63 in squamous cell carcinoma: defining the oncogenic routes affecting epigenetic landscape and tumour microenvironment

Gatti

Fernanda

Annicchiarico-Petruzzelli

et al. 2019

Molecular Oncology

View full text Add to dashboard Cite

Squamous cell carcinoma ( SCC ) is a treatment‐refractory tumour which arises from the epithelium of diverse anatomical sites such as oesophagus, head and neck, lung and skin. Accumulating evidence has revealed a number of genomic, clinical and molecular features commonly observed in SCC of distinct origins. Some of these genetic events culminate in fostering the activity of ΔNp63, a potent oncogene which exerts its pro‐tumourigenic effects by regulating specific transcriptional programmes to sustain malignant cell proliferation and survival. In this review, we will describe the genetic and epigenetic determinants underlying ΔNp63 oncogenic activities in SCC , and discuss some relevant transcriptional effectors of ΔNp63, emphasizing their impact in modulating the crosstalk between tumour cells and tumour microenvironment ( TME ).

show abstract

“…Briefly, 25 mg of chorionic tissue was incubated with proteinase K, ON at 56°C. Then, DNA was extracted using a QIAmp DNA Blood and Tissue Extraction Kit (Qiagen, Milan, Italy; Rotondo et al, 2016). Total DNA from PBMCs was isolated using a QIAmp DNA Mini Extraction Kit (Qiagen) (Rotondo, Bononi et al, 2017).…”

Section: Dna Isolationmentioning

confidence: 99%

Investigation on silent bacterial infections in specimens from pregnant women affected by spontaneous miscarriage

Contini

Rotondo

Magagnoli

et al. 2018

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

Miscarriage is one of the main complications occurring in pregnancy. The association between adverse pregnancy outcomes and silent bacterial infections has been poorly investigated. Ureaplasma parvum and urealiticum, Mycoplasma genitalium and hominis and Chlamydia trachomatis DNA sequences have been investigated by polymerase chain reaction (PCR) methods in chorionic villi tissues and peripheral blood mononuclear cells (PBMCs) from females with spontaneous abortion (SA, n = 100) and females who underwent voluntary interruption of pregnancy (VI, n = 100). U. parvum DNA was detected in 14% and 15% of SA and VI, respectively, with a mean of bacterial DNA load of 1.3 × 10 copy/cell in SA and 2.8 × 10 copy/cell in VI; U. urealiticum DNA was detected in 3% and 2% of SA and VI specimens, respectively, with a mean DNA load of 3.3 × 10 copy/cell in SA and 1.6 × 10 copy/cell in VI; M. hominis DNA was detected in 5% of SA specimens with a DNA load of 1.3 × 10 copy/cell and in 6% of VI specimens with a DNA load of 1.4 × 10 copy/cell; C. trachomatis DNA was detected in 3% of SA specimens with a DNA load of 1.5 × 10 copy/cell and in 4% of VI specimens with a mean DNA load of 1.4 × 10 copy/cell. In PBMCs from the SA and VI groups, Ureaplasma spp, Mycoplasma spp and C. trachomatis DNAs were detected with a prevalence of 1%-3%. Bacteria were investigated, for the first time, by quantitative real-time PCR (qPCR) in chorionic villi tissues and PBMCs from women affected by SA and VI. These data may help to understand the role and our knowledge of the silent infections in SA.

show abstract

Hypermethylation-Induced Inactivation of theIRF6Gene as a Possible Early Event in Progression of Vulvar Squamous Cell Carcinoma Associated With Lichen Sclerosus

Cited by 49 publications

References 15 publications

Molecular heterogeneity in human papillomavirus‐dependent and ‐independent vulvar carcinogenesis

Molecular heterogeneity in human papillomavirus‐dependent and ‐independent vulvar carcinogenesis

ΔNp63 in squamous cell carcinoma: defining the oncogenic routes affecting epigenetic landscape and tumour microenvironment

Investigation on silent bacterial infections in specimens from pregnant women affected by spontaneous miscarriage

Contact Info

Product

Resources

About