Detection of Human Polyomavirus 7 in Human Thymic Epithelial Tumors

Abstract

Introduction Although the molecular genetics possibly underlying the pathogenesis of human thymoma have been extensively studied, its etiology remains poorly understood. Since murine polyomavirus consistently induces thymomas in mice, we assessed the presence of the novel human polyomavirus 7 (HPyV7) in human thymic epithelial tumors. Methods HPyV7-DNA Fluorescence in situ hybridization (FISH), DNA-PCR and immuno-histochemistry (IHC) were performed in 37 thymomas. Of these, 26 were previously diagnosed with myasthenia gravis (MG). In addition, 20 thymic hyperplasias and 20 fetal thymic tissues were tested. Results HPyV7-FISH revealed specific nuclear hybridization signals within the neoplastic epithelial cells of 23 thymomas (62.2%). With some exceptions, the HPyV7-FISH data correlated with the HPyV7-DNA PCR. By IHC large T antigen (LTAg) expression of HPyV7 was detected, and double staining confirmed its expression in the neoplastic epithelial cells. Eighteen of the 26 MG-positive and 7 of the 11 MG-negative thymomas were HPyV7-positive. 40% of the 20 hyperplastic thymi were HPyV7-positive by PCR as confirmed by FISH and IHC in the follicular lymphocytes. All 20 fetal thymi tested HPyV7-negative. Conclusions The presence of HPyV7-DNA and LTAg expression in the majority of thymomas possibly link HPyV7 to human thymomagenesis. Further investigations are needed to elucidate the possible associations of HPyV7 and MG.

The 2015 World Health Organization Classification of Tumors of the Thymus: Continuity and Changes

“…88 If confirmed, this might have an impact on the classification of TETs and their clinical management.…”

Cutaneous Human Polyomavirus Small T Antigens and 4E-BP1 Targeting

“…This finding suggests a novel mechanism of 4E-BP1 in HPyV7 pathogenesis and provides evidence supporting a possible role for the virus in neoplastic cell growth. Although HPyV7 infection has been associated with epithelial thymomas and pruritic dermal rash, its specific roles in cutaneous diseases remain largely undefined [4,5]. In this context, it is notable that 4E-BP1 hyperphosphorylation correlates with aggressive cancer growth and worse prognosis for metastatic melanoma patients [9,15,16].…”

“…While MCPyV is, to date, the only oncogenic virus of the polyomavirus family, trichodysplasia spinulosa-associated polyomavirus (TSPyV), human polyomavirus 6 (HPyV6), and human polyomavirus 7 (HPyV7) have all been associated with hyperproliferative epithelial growths. Currently, TSPyV, HPyV6, and HPyV7 are implicated in the development and progression of trichodysplasia spinulosa, the neoplastic growth of keratinocytes in response to BRAF inhibitors, and the pathogenesis of human thymic epithelial tumors, respectively [2,3,4,5]. …”

Early and late promoters of BK polyomavirus, Merkel cell polyomavirus, Trichodysplasia spinulosa-associated polyomavirus and human polyomavirus 12 are among the strongest of all known human polyomaviruses in 10 different cell lines

“…BKPyV is associated with nephropathy in renal transplant patients and with haemorrhagic cystitis in bone marrow recipients (Hirsch & Steiger, 2003), while JCPyV is the aetiological agent of progressive multifocal leukoencephalopathy (Tan & Koralnik, 2010 cause of 80 % of Merkel cell carcinoma (Feng et al, 2008), while TSPyV is linked to the rare skin disease trichodysplasia spinulosa in immunocompromised patients (van der Meijden et al, 2010). HPyV7 DNA was discovered in peripheral blood of two and in gastric mucosal tissues of one of two lung transplant patients who developed pruritic rash, and DNA and large T-antigen expression was found to be common in thymomas (23/37) and thymic hyperplasias (8/20) (Ho et al, 2015;Rennspiess et al, 2015). Whether the other HPyVs contribute to diseases is not known (DeCaprio & Garcea, 2013).…”