Merkel Cell Polyomavirus-positive Merkel Cell Carcinoma in a Patient with Epidermodysplasia Verruciformis

Mizuno, Yuki; Kato, Go; Shu, En; Ohnishi, Hiroyuki; Fukao, Toshiyuki; Ohara, Osamu; Fukumoto, Hiroki; Katano, Harutaka; Seishima, Mariko

doi:10.2340/00015555-1868

Cited by 6 publications

(3 citation statements)

References 11 publications

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“…Sixty-four percent of cases with EV (16/25) originated from consanguineous families, and 48% (12/25) of EV patients developed NMSC (such as SCC and/or basal cell carcinoma) before 61 years of age, of which the youngest patient suffered from BCC at 22 years of age. One patient with TMC8 variants suffered from Merkel cell carcinoma at 82 years of age ( Mizuno et al, 2015 ). Consistent with the previous report by Imahorn et al (2017) , the most frequent EV-HPV in the 25 patients was HPV-5 (12/25), followed by HPV-14 (7/25) and HPV-20 (4/25), and the rare EV-HPVs included HPV-17, 22, 38, 93, 3, 8, 9, 12, 21–24, 47, and so on.…”

Section: Discussionmentioning

confidence: 99%

Identification and Splicing Characterization of Novel TMC6 and TMC8 Variants Associated With Epidermodysplasia Verruciformis in Three Chinese Families

et al. 2021

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Background: Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by abnormal susceptibility to human beta papillomavirus infections and a particular propensity to develop non-melanoma skin cancers (NMSCs). The majority of EV cases are caused by biallelic null variants in TMC6, TMC8, and CIB1. This study aimed to identify disease-causing variants in three Chinese families with EV and to elucidate their molecular pathogenesis.Methods: Genomic DNA from the probands of three EV families was analyzed by whole-exome sequencing (WES). cDNA sequencing was performed to investigate abnormal splicing of the variants. Quantitative RT-PCR (qRT-PCR) was conducted to quantify the mRNA expression of mutant TMC6 and TMC8.Results: Whole-exome sequencing identified two novel homozygous variants (c.2278-2A > G in TMC6 and c.559G > A in TMC8) in families 1 and 2, respectively. In family 3, WES revealed a recurrent and a novel compound heterozygous variant, c.559G > A and c.1389G > A, in TMC8. The c.2278-2A > G TMC6 variant led to the skipping of exon 19 and resulted in premature termination at codon 776. Subsequent qRT-PCR revealed that the aberrantly spliced transcript was partly degraded. Notably, the TMC8 c.559G > A variant created a novel acceptor splice site at c.561 and yielded three different aberrant transcripts. qRT-PCR revealed that most of the mutant transcripts were degraded via nonsense-mediated mRNA decay (NMD).Conclusion: We identified three novel disease-causing variants in TMC6 or TMC8 in three Chinese families with EV. The EV phenotypes of the three patients were due to a reduction in TMC6 or TMC8. Our findings expand the genetic causes of EV in the Chinese population.

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Section: Discussionmentioning

confidence: 99%

Identification and Splicing Characterization of Novel TMC6 and TMC8 Variants Associated With Epidermodysplasia Verruciformis in Three Chinese Families

et al. 2021

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“…MCPyV positive MCC has been found in patients with EV and one study showed a strong association of EV‐associated skin neoplasms with MCPyV which suggests a unique susceptibility to infections with MCPyV in these keratinocyte disorders 256–258 …”

Section: Augmented Induction Of Malignancymentioning

confidence: 99%

Rubella virus chronic inflammatory disease and other unusual viral phenotypes in inborn errors of immunity

Kilich,

Perelygina,

Sullivan

2023

Immunological Reviews

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SummaryInfectious susceptibility is a component of many inborn errors of immunity. Nevertheless, antibiotic use is often used as a surrogate in history taking for infectious susceptibility, thereby disadvantaging patients who present with viral infections as their phenotype. Further complicating clinical evaluations are unusual manifestations of viral infections which may be less familiar that the typical respiratory viral infections. This review covers several unusual viral phenotypes arising in patients with inborn errors of immunity and other settings of immune compromise. In some cases, chronic infections lead to oncogenesis or tumor‐like growths and the conditions and mechanisms of viral‐induced oncogenesis will be described. This review covers enterovirus, rubella, measles, papillomavirus, and parvovirus B19. It does not cover EBV and hemophagocytic lymphohistiocytosis nor lymphomagenesis related to EBV. EBV susceptibility has been recently reviewed. Our goal is to increase awareness of the unusual manifestations of viral infections in patients with IEI and to describe treatment modalities utilized in this setting. Coincidentally, each of the discussed viral infections can have a cutaneous component and figures will serve as a reminder of the physical features of these viruses. Given the high morbidity and mortality, early recognition can only improve outcomes.

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“…Several other research groups confirmed the Merkel cell polyomavirus (MCPyV) presence in MCC, although the viral prevalence in MCC varies around the world. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] This HPyV was the first and, so far, the only HPyV to be etiologically related to a neoplasia in humans. Since its discovery, the scientific curiosity on polyomaviruses, especially regarding their relationship to human cancer, has been reignited.…”

Section: Introductionmentioning

confidence: 99%

Human Polyomaviruses: The Battle of Large and Small Tumor Antigens

et al. 2017

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About 40 years ago, the large and small tumor antigens (LT-Ag and sT-Ag) of the polyomavirus (PyVs) simian vacuolating virus 40 have been identified and characterized. To date, it is well known that all the discovered human PyVs (HPyVs) encode these 2 multifunctional and tumorigenic proteins, expressed at viral replication early stage. The 2 T-Ags are able to transform cells both in vitro and in vivo and seem to play a distinct role in the pathogenesis of some tumors in humans. In addition, they are involved in viral DNA replication, transcription, and virion assembly. This short review focuses on the structural and functional features of the HPyVs’ LT-Ag and sT-Ag, with special attention to their transforming properties.

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Merkel Cell Polyomavirus-positive Merkel Cell Carcinoma in a Patient with Epidermodysplasia Verruciformis

Cited by 6 publications

References 11 publications

Identification and Splicing Characterization of Novel TMC6 and TMC8 Variants Associated With Epidermodysplasia Verruciformis in Three Chinese Families

Identification and Splicing Characterization of Novel TMC6 and TMC8 Variants Associated With Epidermodysplasia Verruciformis in Three Chinese Families

Rubella virus chronic inflammatory disease and other unusual viral phenotypes in inborn errors of immunity

Human Polyomaviruses: The Battle of Large and Small Tumor Antigens

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