Fluorescence in situ hybridization confirms the presence of Merkel cell polyomavirus in chronic lymphocytic leukemia cells

Haugg, Anke; Speel, Ernst‐Jan M.; Pantulu, Naga Deepa; Pallasch, Christian P.; Kurz, Anna Kordelia; Kvasnicka, Hans Michael; Cathomas, Gieri; Wendtner, Clemens‐Martin; Hausen, Axel zur

doi:10.1182/blood-2011-03-339895

Cited by 31 publications

(28 citation statements)

References 5 publications

(14 reference statements)

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“…A lack of association of MCPyV with CLL is consistent with the low DNA and LT-Ag presence in CLL subjects (Shuda et al, 2009;Toracchio et al, 2009;Teman et al, 2011;Comar et al, 2012;Imajoh et al, 2012;Cimino et al, 2013), but a plausible explanation is needed for the previous findings encouraging an association (Haugg et al, 2011;Pantulu et al, 2010). The mutated sequence of MCPyV LT-Ag in the nucleus of CLL cells was only detected in six (8 %) out of 70 samples previously purified to contain mainly CD19 + /CD5 CLL cells.…”

Section: Received 9 January 2015supporting

confidence: 62%

“…The overall low prevalences (2-36 %) of viral DNA and large T-antigen (LT-Ag) detected in tumour tissue or peripheral blood mononuclear cells of CLL subjects (Shuda et al, 2009;Toracchio et al, 2009;Teman et al, 2011;Comar et al, 2012;Imajoh et al, 2012;Cimino et al, 2013) do not support an aetiological role. However, the presence of a truncated LT-Ag MCPyV sequence in the nucleus, a peculiarity of MCPyV in Merkel cell carcinoma cells, has been reported in highly purified CD19 + /CD5 + CLL cells (Haugg et al, 2011;Pantulu et al, 2010). Serology data are furthermore inconsistent; in a previous case-control study we identified an increased MCPyV seroprevalence in CLL patients (Robles et al, 2012) whereas in a recent paper a decreased risk was observed (Teras et al, 2015), although none of them significant.…”

Section: Received 9 January 2015mentioning

confidence: 64%

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Seroreactivity against Merkel cell polyomavirus and other polyomaviruses in chronic lymphocytic leukaemia, the MCC-Spain study

Robles

Casabonne

Benavente

et al. 2015

Journal of General Virology

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Merkel cell polyomavirus (MCPyV) has been suspected to cause chronic lymphocytic leukaemia (CLL) but previous data are inconsistent. We measured seroreactivities of nine polyomaviruses (MCPyV, BKPyV, JCPyV, LPyV, KIPyV, WUPyV, HPyV-6, HPyV-7 and TSPyV) in 359 CLL cases and 370 controls using bead-based multiplex serology technology. We additionally tested two herpesviruses (HSV-1 and CMV). Associations between disease and viral seroreactivities were assessed using logistic regression. All human viruses showed high seroprevalences (69-99 %) against structural proteins in controls but significantly lower viral seroprevalences in cases (58-94 %; OR range50.21-0.70, P value ,0.05), except for MCPyV

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Section: Received 9 January 2015supporting

confidence: 62%

Section: Received 9 January 2015mentioning

confidence: 64%

Seroreactivity against Merkel cell polyomavirus and other polyomaviruses in chronic lymphocytic leukaemia, the MCC-Spain study

Robles

Casabonne

Benavente

et al. 2015

Journal of General Virology

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“…However, CM2B4 has been shown to have limited sensitivity relative to qPCR (14,31). Other methods that have also been reported in the literature include fluorescence in situ hybridization (FISH) and IsHyb ISH (32)(33)(34). However, the interpretation/reporting of FISH results can be challenging.…”

Section: Discussionmentioning

confidence: 99%

Age and Gender Associations of Virus Positivity in Merkel Cell Carcinoma Characterized Using a Novel RNA In Situ Hybridization Assay

Wang

Harms

Palanisamy

et al. 2017

Clinical Cancer Research

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Purpose-Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine tumor of the skin. Merkel cell polyomavirus (MCPyV) plays an oncogenic role in the majority of MCCs. Detection of MCPyV in MCCs has diagnostic utility and prognostic potential. We investigated whether RNAscope, an RNA in situ hybridization (ISH) assay for detection of RNA transcripts in tissues, is useful for MCPyV detection.Experimental Design-We applied an RNAscope probe targeting MCPyV T antigen transcripts on tissue microarrays (TMAs) and whole tissue sections encompassing 87 MCCs from 75 patients, 14 carcinomas of other types, and benign tissues. For comparison, quantitative PCR (qPCR) was performed on 57 cases of MCC from 52 patients.Results-RNA-ISH demonstrated the presence of MCPyV in 37/75 (49.3%) cases. Notably, tumors from younger patients (< 73 years) had a significantly higher virus positivity than those from elderly patients (≥ 73 years) (64.9% vs. 34.2%, P =0.011). Female patients had a higher positive rate of MCPyV than male patients (66.7% vs. 39.6%, P =0.032). Data from both RNA- HHMI Author Manuscript HHMI Author Manuscript HHMI Author Manuscriptdetermining MCPyV status, RNAscope had 100% sensitivity and 100% specificity. There was a strong correlation between qPCR copy number and RNA-ISH product score (Spearman's correlation coefficient R 2 = 0.932, P < 0.0001).Conclusions-RNA-ISH is comparably sensitive to qPCR for detection of MCPyV and allows for correlation with tissue morphology. This study also reveals a significant association between age, gender, and MCPyV positivity.

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“…Since 2008, MCPyV DNA has been detected in approximately 80% of more than 1000 MCCs yet tested. MCPyV has been shown to be integrated in the MCC genomes by diverse molecular techniques (2)(3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Early B-Cell Differentiation in Merkel Cell Carcinomas: Clues to Cellular Ancestry

et al. 2013

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Fluorescence in situ hybridization confirms the presence of Merkel cell polyomavirus in chronic lymphocytic leukemia cells

Cited by 31 publications

References 5 publications

Seroreactivity against Merkel cell polyomavirus and other polyomaviruses in chronic lymphocytic leukaemia, the MCC-Spain study

Seroreactivity against Merkel cell polyomavirus and other polyomaviruses in chronic lymphocytic leukaemia, the MCC-Spain study

Age and Gender Associations of Virus Positivity in Merkel Cell Carcinoma Characterized Using a Novel RNA In Situ Hybridization Assay

Early B-Cell Differentiation in Merkel Cell Carcinomas: Clues to Cellular Ancestry

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