Merkel cell carcinoma: Do you know your guidelines?

Miles, Brett A.; Goldenberg, David

doi:10.1002/hed.24359

Cited by 16 publications

(5 citation statements)

References 118 publications

(273 reference statements)

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“…More VN- and VP-MCC should be scrutinized to establish whether STING is specifically silenced in the VP-MCC and the potential role of T antigens in silencing STING should be explored. Postsurgical adjuvant radiation is common in the treatment of MCC patients and although adjuvant radiotherapy can improve locoregional control with reduced recurrence rate of the tumor, it may not affect overall survival [ 216 , 217 , 218 , 219 ]. Whether VN- and VP-MCC patients display different sensitivity to radiation is not known, but a previous study had shown that absence of STING impaired radiation-mediated tumor regression [ 220 ].…”

Section: Immune Evasion Of Vp-mccmentioning

confidence: 99%

Merkel Cell Polyomavirus and Merkel Cell Carcinoma

Pietropaolo¹,

Prezioso

Moens

2020

Cancers

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Viruses are the cause of approximately 15% of all human cancers. Both RNA and DNA human tumor viruses have been identified, with Merkel cell polyomavirus being the most recent one to be linked to cancer. This virus is associated with about 80% of Merkel cell carcinomas, a rare, but aggressive cutaneous malignancy. Despite its name, the cells of origin of this tumor may not be Merkel cells. This review provides an update on the structure and life cycle, cell tropism and epidemiology of the virus and its oncogenic properties. Putative strategies to prevent viral infection or treat virus-positive Merkel cell carcinoma patients are discussed.

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Section: Immune Evasion Of Vp-mccmentioning

confidence: 99%

Merkel Cell Polyomavirus and Merkel Cell Carcinoma

Pietropaolo¹,

Prezioso

Moens

2020

Cancers

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“…Merkel cell carcinoma (MCC) is a rare but highly aggressive skin cancer occurring predominantly in elderly and immunosuppressed patients. The tumor shows a high propensity to metastasize, which is reflected in a poor 5 year survival rate [1][2][3][4][5]. The majority of MCCs (~60-80% in the northern hemisphere) are causally linked to infection with Merkel cell polyomavirus (MCPyV).…”

Section: Introductionmentioning

confidence: 99%

High-resolution analysis of Merkel Cell Polyomavirus in Merkel Cell Carcinoma reveals distinct integration patterns and suggests NHEJ and MMBIR as underlying mechanisms

et al. 2020

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Merkel Cell Polyomavirus (MCPyV) is the etiological agent of the majority of Merkel Cell Carcinomas (MCC). MCPyV positive MCCs harbor integrated, defective viral genomes that constitutively express viral oncogenes. Which molecular mechanisms promote viral integration, if distinct integration patterns exist, and if integration occurs preferentially at loci with specific chromatin states is unknown. We here combined short and long-read (nanopore) next-generation sequencing and present the first high-resolution analysis of integration site structure in MCC cell lines as well as primary tumor material. We find two main types of integration site structure: Linear patterns with chromosomal breakpoints that map closely together, and complex integration loci that exhibit local amplification of genomic sequences flanking the viral DNA. Sequence analysis suggests that linear patterns are produced during viral replication by integration of defective/linear genomes into host DNA double strand breaks via non-homologous end joining, NHEJ. In contrast, our data strongly suggest that complex integration patterns are mediated by microhomology-mediated break-induced replication, MMBIR. Furthermore, we show by ChIP-Seq and RNA-Seq analysis that MCPyV preferably integrates in open chromatin and provide evidence that viral oncogene expression is driven by the viral promoter region, rather than transcription from juxtaposed host promoters. Taken together, our data explain the characteristics of MCPyV integration and may also provide a model for integration of other oncogenic DNA viruses such as papillomaviruses.

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“…The poor outcomes in patients with metastatic MCC calls for more efficacious treatment options in the new horizon of precision medicine. Wide local excision is the primary treatment for localized primary MCC requiring negative margins of 1 to 2 cm . While there are mixed recommendations regarding postsurgical adjuvant radiation, this therapy remains the current guideline as the standard of care with several studies demonstrating reduced recurrence and improved survival .…”

Section: Discussionmentioning

confidence: 99%

“…Wide local excision is the primary treatment for localized primary MCC requiring negative margins of 1 to 2 cm . While there are mixed recommendations regarding postsurgical adjuvant radiation, this therapy remains the current guideline as the standard of care with several studies demonstrating reduced recurrence and improved survival . In patients who are not surgical candidates, radiotherapy alone or combined with systemic therapy has shown to extend life to some degree.…”

Section: Discussionmentioning

confidence: 99%

Cancer‐testis antigens as biomarkers for Merkel cell carcinoma: Pitfalls and opportunities

et al. 2019

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Background: The prognosis and treatment options for metastatic Merkel cell carcinoma (MCC) are poor. The immune-privileged status of cancer-testis (CT) antigens imparts tumor specificity, making them ideal candidates for targeted immunotherapy. We investigate the usefulness of the CT antigens SPA17 (sperm protein-17 [SP-17]), IGF2BP3 (insulin-like growth factor-II mRNA-binding protein 3 [IMP-3]), and transmembrane protein with epidermal growth factor (EGF)-like and two follistatin-like domains 1 (TMEFF1) as potential MCC biomarkers and evaluate their possible utility in immunotherapy and molecularly targeted image-guided treatment. Methods: The CT antigens SP-17, IMP-3, and TMEFF1 were selected using transcriptome profiling to identify CT antigens expressed in MCC tumors. Antibodies directed against these CT antigens were stained. Twelve normal skin tissue samples were used as a control. The average percentage of positive cells in each tumor was computed. Results: Twelve of 14 (86%) MCC cases showed crisp nuclear staining for SP-17, with 2.06% of cells staining positive. IMP-3 showed crisp, perinuclear staining in all 14 MCC cases, with 52.93% MCC cells staining positive. TMEFF1 showed perinuclear staining in all 14 MCC cases, with 96.51% of tumor cells staining positive.Conclusions: CT antigens were found to be expressed in both MCC and some control tissues. SP-17 was the most specific yet the least sensitive. IMP-3 and TMEFF1 were both sensitive but not specific. CT antigens may represent valuable treatment targets in MCC. K E Y W O R D Simmunohistochemistry, IMP-3, Merkel cell carcinoma, SP-17, TMEFF1

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Merkel cell carcinoma: Do you know your guidelines?

Abstract: The pathogenesis of MCC has recently been impacted with the discovery of the Merkel cell polyomavirus (MCPyV). Research to establish targeted and immunologic therapeutic options are ongoing.

Cited by 16 publications

References 118 publications

Merkel Cell Polyomavirus and Merkel Cell Carcinoma

Merkel Cell Polyomavirus and Merkel Cell Carcinoma

High-resolution analysis of Merkel Cell Polyomavirus in Merkel Cell Carcinoma reveals distinct integration patterns and suggests NHEJ and MMBIR as underlying mechanisms

Cancer‐testis antigens as biomarkers for Merkel cell carcinoma: Pitfalls and opportunities

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