Expression of Retroelements in Cervical Cancer and Their Interplay with HPV Infection and Host Gene Expression

Curty, Gislaine; Menezes, Albert N.; Brant, Ayslan Castro; Rougvie, Miguel de Mulder; Moreira, Miguel Ângelo Martins; Soares, Marcelo A.

doi:10.3390/cancers13143513

Cited by 8 publications

(9 citation statements)

References 49 publications

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“…This is in line with preclinical data. Curty et al (19) have reported that the expression of different LINE-1 elements was modulated by the type and number of HPV strains. In clinical routine, this can be neglected as p16 is a reliable surrogate marker of high-risk HPV infection.…”

Section: Distinct Orf1p Expression Was Present In the Vast Majority O...mentioning

confidence: 99%

ORF1p Is a Potential Novel Diagnostic Marker for Differentiated Vulvar Intraepithelial Neoplasia

Hofstetter

Mildner

Tschandl

et al. 2022

International Journal of Gynecological Pathology

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Accurate diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN) can be challenging as histomorphologic features may be subtle and overlap with nondysplastic lesions. In practice, aberrant p53 expression supports the diagnosis, but a substantial percentage retains wild-type p53. Recently, the retrotransposon long interspersed nuclear element 1 has been detected in distinct cancer types. We have now investigated the expression of the long interspersed nuclear element 1 encoded protein ORF1p in dysplastic and nondysplastic vulvar samples to assess its diagnostic value. Specimens of dVIN (n=29), high-grade squamous intraepithelial lesions (n=26), inflammatory vulvar lesions (n=20), lichen sclerosus (n=22), and normal vulvar epithelia (n=29) were included. ORF1p and p53 expression was determined using immunohistochemistry. The majority of dVIN [27/29 (93%)] and high-grade squamous intraepithelial lesions [20/26 (77%)] showed distinct (i.e. moderate or strong) ORF1p expression in the basal and suprabasal or all epithelial layers, respectively. Of note, ORF1p was present in all 4 cases of dVIN with wild-type p53 staining pattern. In contrast, ORF1p was negative or weakly expressed in most inflammatory lesions [14/20 (70%)] and lichen sclerosus [18/22 (82%), P<0.001]. Normal control epithelium exhibited negative staining in all cases. In conclusion, ORF1p might be a useful diagnostic marker for dVIN, especially in cases with retained wild-type p53.

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Section: Distinct Orf1p Expression Was Present In the Vast Majority O...mentioning

confidence: 99%

ORF1p Is a Potential Novel Diagnostic Marker for Differentiated Vulvar Intraepithelial Neoplasia

Hofstetter

Mildner

Tschandl

et al. 2022

International Journal of Gynecological Pathology

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“…HPV integration sites within the human genome have been closely scrutinised with reported changes in gene and protein expression near integration hot spots as well as differential pathway activation [27][28][29]. Possible mechanisms include differences in promoter methylation, which have also been reported in HPV positive versus negative lesions [30][31][32], direct disruption of genes, or activation of retroelements [33].…”

Section: Hpv-associated Pathogenesismentioning

confidence: 99%

Genomic Risk Factors for Cervical Cancer

Ramachandran

Dörk

2021

Cancers

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Cervical cancer is the fourth common cancer amongst women worldwide. Infection by high-risk human papilloma virus is necessary in most cases, but not sufficient to develop invasive cervical cancer. Despite a predicted genetic heritability in the range of other gynaecological cancers, only few genomic susceptibility loci have been identified thus far. Various case-control association studies have found corroborative evidence for several independent risk variants at the 6p21.3 locus (HLA), while many reports of associations with variants outside the HLA region remain to be validated in other cohorts. Here, we review cervical cancer susceptibility variants arising from recent genome-wide association studies and meta-analysis in large cohorts and propose 2q14 (PAX8), 17q12 (GSDMB), and 5p15.33 (CLPTM1L) as consistently replicated non-HLA cervical cancer susceptibility loci. We further discuss the available evidence for these loci, knowledge gaps, future perspectives, and the potential impact of these findings on precision medicine strategies to combat cervical cancer.

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“…HPV integration sites within the human genome have been closely scrutinized with reported changes in gene and protein expression near integration hot spots, as well as differential pathway activation [27][28][29]. Possible mechanisms include differences in promoter methylation which have also been reported in HPV positive versus negative lesions [30][31][32], direct disruption of genes, or activation of retroelements [33].…”

Section: Hpv-associated Pathogenesismentioning

confidence: 99%

Genomic Risk Factors for Cervical Cancer

Ramachandran¹,

Dörk²

2021

Preprint

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Cervical cancer is the fourth common cancer amongst women worldwide. Environmental factors such as smoking and obesity, and recurrent infection by high-risk human papillomavirus subtypes are known to promote progression towards invasive cervical disease. Infection by high-risk HPV is necessary in most cases but not sufficient to develop invasive cervical cancer. Despite a predicted genetic heritability of between 27-36%, known genetic susceptibility loci that may be tumorigenic or influence host response to infection, only account for a small fraction of heritable risk factors so far. Various biobank-driven population based studies and meta-analyses have found corroborative evidence for several risk variants at the 6p21.3 locus (HLA), while many reports of variants outside the HLA region remain to be validated in other cohorts. Here, we review cervical cancer susceptibility variants arising from recent genome-wide association studies and meta-analysis in large cohorts and propose 2q14 (PAX8), 17q12 (GSDMB), and 5p15.33 (CLPTM1L) as consistently replicated non-HLA cervical cancer susceptibility loci. We further discuss the available evidence for these loci, knowledge gaps, future perspectives, and the potential impact of these findings on precision medicine strategies to combat cervical cancer.

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Expression of Retroelements in Cervical Cancer and Their Interplay with HPV Infection and Host Gene Expression

Cited by 8 publications

References 49 publications

ORF1p Is a Potential Novel Diagnostic Marker for Differentiated Vulvar Intraepithelial Neoplasia

ORF1p Is a Potential Novel Diagnostic Marker for Differentiated Vulvar Intraepithelial Neoplasia

Genomic Risk Factors for Cervical Cancer

Genomic Risk Factors for Cervical Cancer

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