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C‐terminal deletions of Merkel cell polyomavirus large T‐antigen, a highly specific surrogate marker for virally induced malignancy
Author(s) -
Schmitt Markus,
Wieland Ulrike,
Kreuter Alexander,
Pawlita Michael
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27607
Subject(s) - merkel cell polyomavirus , biology , merkel cell carcinoma , merkel cell , polyomavirus infections , virology , virus , microbiology and biotechnology , genetics , kidney , bk virus , carcinoma , kidney transplantation
In 67–100% of cutaneous Merkel cell carcinomas (MCC) the Merkel cell polyomavirus (MCPyV) integrates into the host genome. Mutations and deletions truncating the C‐terminal helicase domain of the T‐antigen (TAg) protein have been detected in these MCCs, but not in healthy skin specimens. C‐terminal deletions of the TAg nucleic acid sequences are characteristic for about 38% of these cases. While the association of MCPyV with MCC has been proven, it is unknown whether MCPyV may play a similar role in other tumor entities. We describe in detail the development and validation of a novel Merkel cell polyomavirus TAg C‐terminus deletion assay (MCPyV ΔC‐TAg). The triplex real‐time PCR quantifies the N‐ and C‐terminal part of the MCPyV TAg gene and the cellular β‐globin gene. By comparing the copy numbers of the N‐ and C‐terminal part, deletions of the MCPyV TAg C‐terminus are rapidly identified. MCPyV ΔC‐TAg was used to assess the physical state of MCPyV TAg in a large series of 55 MCCs, 15 cutaneous lymphomas and 47 forehead smears of healthy individuals. Neither DNA positivity nor viral load was able to discriminate MCCs from the other different types of samples. However, deleted TAg C‐terminus sequences were detected only in MCPyV positive MCCs (39%). Consequently, detection of deleted C‐terminal TAg sequences appears to be a highly specific surrogate marker for virally induced malignancy and should be used to support novel assumed MCPyV–tumor associations. The study further supports the notion that MCPyV does not play a role in cutaneous lymphoma pathogenesis.