Genomic characterization of vulvar squamous cell carcinoma

Alawi, Malik; Oliveira‐Ferrer, Leticia; Jaeger, Anna; Eylmann, Kathrin; Burandt, Eike; Schmalfeldt, Barbara; Joosse, Simon A.; Woelber, Linn

doi:10.1016/j.ygyno.2020.06.482

Cited by 21 publications

(32 citation statements)

References 30 publications

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“…These subtypes are also known to differ in their epidemiological, clinical, pathological, and molecular characteristics. For example, HPV-associated VSCC, the less prevalent subtype, affects women of 50–60 years of age, and is associated with a favorable prognosis [ 7 , 8 ]. In contrast, the more prevalent HPV-independent VSCC usually develops on the background of chronic dermatoses in women of >70 years of age, and is associated with high rates of recurrence [ 2 , 5 , 6 , 7 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…For example, HPV-associated VSCC, the less prevalent subtype, affects women of 50–60 years of age, and is associated with a favorable prognosis [ 7 , 8 ]. In contrast, the more prevalent HPV-independent VSCC usually develops on the background of chronic dermatoses in women of >70 years of age, and is associated with high rates of recurrence [ 2 , 5 , 6 , 7 , 9 ]. On a molecular level, somatic mutations of TP53 have been frequently detected in HPV-independent VSCCs, and have been implicated as the ‘oncogenic driver’ for this subtype [ 7 , 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, the more prevalent HPV-independent VSCC usually develops on the background of chronic dermatoses in women of >70 years of age, and is associated with high rates of recurrence [ 2 , 5 , 6 , 7 , 9 ]. On a molecular level, somatic mutations of TP53 have been frequently detected in HPV-independent VSCCs, and have been implicated as the ‘oncogenic driver’ for this subtype [ 7 , 10 , 11 , 12 ]. However, recent studies have discovered molecular heterogeneity among HPV-independent VSCCs, as some of these tumors can be TP53 wild-type, and harbor HRAS or NOTCH1 mutations instead [ 7 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Exploring Differentially Methylated Genes in Vulvar Squamous Cell Carcinoma

Dasgupta

Ewing‐Graham

Swagemakers

et al. 2021

Cancers

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DNA methylation is the most widely studied mechanism of epigenetic modification, which can influence gene expression without alterations in DNA sequences. Aberrations in DNA methylation are known to play a role in carcinogenesis, and methylation profiling has enabled the identification of biomarkers of potential clinical interest for several cancers. For vulvar squamous cell carcinoma (VSCC), however, methylation profiling remains an under-studied area. We sought to identify differentially methylated genes (DMGs) in VSCC, by performing Infinium MethylationEPIC BeadChip (Illumina) array sequencing, on a set of primary VSCC (n = 18), and normal vulvar tissue from women with no history of vulvar (pre)malignancies (n = 6). Using a false-discovery rate of 0.05, beta-difference (Δβ) of ± 0.5, and CpG-island probes as cut-offs, 199 DMGs (195 hyper-methylated, 4 hypo-methylated) were identified for VSCC. Most of the hyper-methylated genes were found to be involved in transcription regulator activity, indicating that disruption of this process plays a vital role in VSCC development. The majority of VSCCs harbored amplifications of chromosomes 3, 8, and 9. We identified a set of DMGs in this exploratory, hypothesis-generating study, which we hope will facilitate epigenetic profiling of VSCCs. Prognostic relevance of these DMGs deserves further exploration in larger cohorts of VSCC and its precursor lesions.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exploring Differentially Methylated Genes in Vulvar Squamous Cell Carcinoma

Dasgupta

Ewing‐Graham

Swagemakers

et al. 2021

Cancers

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“…Vulvar squamous cell carcinoma (VSCC) constitutes 90% of all vulvar malignancies, and its incidence has risen over the past decades (1,2). Approximately 25% of VSCCs arise in association with a human papillomavirus (HPV)-infection, via the precursor lesion, high grade squamous intraepithelial lesion (HSIL) (3).…”

Section: Introductionmentioning

confidence: 99%

“…The dual pathogenesis of VSCC has been recognized several years ago, however, molecular mechanisms of the carcinogenesis have not been well characterized (4). This is largely because the genomic profiles of VSCC or its precursor lesions have been investigated in only a few studies so far (1,(5)(6)(7)(8)(9)(10)(11). These studies identified somatic mutations of TP53 to be the pivotal oncogenic driver of HPV-independent VSCC, and also detected genomic alterations of PIK3CA, HRAS, or FGFR3 in both subtypes of VSCC (7)(8)(9)11).…”

Section: Introductionmentioning

confidence: 99%

Nuclear factor IB is downregulated in vulvar squamous cell carcinoma (VSCC): Unravelling differentially expressed genes in VSCC through gene expression dataset analysis

et al. 2021

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Vulvar squamous cell carcinoma (VSCC) comprises two distinct etiopathological subtypes: i) Human papilloma virus (HPV)-related VSCC, which arises via the precursor high grade squamous intraepithelial lesion (HSIL); and ii) HPV-independent VSCC, which arises via precursor, differentiated vulvar intraepithelial neoplasia (dVIN), driven by TP53 mutations. However, the mechanism of carcinogenesis of VSCC is poorly understood. The current study aimed to gain insight into VSCC carcinogenesis by identifying differentially expressed genes (DEGs) for each VSCC subtype. The expression of certain DEGs was then further assessed by performing immunohistochemistry (IHC) on whole tissue sections of VSCC and its precursors. Statistical analysis of microarrays was performed on two independent gene expression datasets (GSE38228 and a study from Erasmus MC) on VSCC and normal vulva. DEGs were identified that were similarly (up/down) regulated with statistical significance in both datasets. For HPV-related VSCCs, this constituted 88 DEGs, and for HPV-independent VSCCs, this comprised 46 DEGs. IHC was performed on VSCC (n=11), dVIN (n=6), HSIL (n=6) and normal vulvar tissue (n=7) with i) signal transducer and activator of transcription 1 (STAT1; an upregulated DEGs); ii) nuclear factor IB (NFIB; a downregulated DEG); iii) p16 (to determine the HPV status of tissues); and iv) p53 (to confirm the histological diagnoses). Strong and diffuse NFIB expression was observed in the basal and para-basal layers of normal vulvar tissue, whereas NFIB expression was minimal or completely negative in dVIN and in both subtypes of VSCC. In contrast, no discernable difference was observed in STAT1 expression among normal vulvar tissue, dVIN, HSIL or VSCC. By leveraging bioinformatics, the current study identified DEGs that can facilitate research into VSCC carcinogenesis. The results suggested that NFIB is downregulated in VSCC and its relevance as a diagnostic/prognostic biomarker deserves further exploration.

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Vulval Squamous Cell Carcinoma

Beurden¹

2022

Ridley's the Vulva

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Genomic characterization of vulvar squamous cell carcinoma

Cited by 21 publications

References 30 publications

Exploring Differentially Methylated Genes in Vulvar Squamous Cell Carcinoma

Exploring Differentially Methylated Genes in Vulvar Squamous Cell Carcinoma

Nuclear factor IB is downregulated in vulvar squamous cell carcinoma (VSCC): Unravelling differentially expressed genes in VSCC through gene expression dataset analysis

Vulval Squamous Cell Carcinoma

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