Comparable expression and phosphorylation of the retinoblastoma protein in Merkel cell polyoma virus positive and negative Merkel cell carcinoma

  title={Comparable expression and phosphorylation of the retinoblastoma protein in Merkel cell polyoma virus positive and negative Merkel cell carcinoma},
  author={Roland Houben and David Schrama and Miriam Alb and Claudia Pf{\"o}hler and Uwe Trefzer and Selma Ugurel and J{\"u}rgen Christian Becker},
  journal={International Journal of Cancer},
Dear Editor, It has been demonstrated, that DNA from the Merkel cell polyoma virus (MCV) is monoclonally integrated in the genome of Merkel cell carcinoma (MCC) cells in the majority of tumors. In this respect, Bathia et al. recently reported an observation in THE JOURNAL which suggests that two subgroups of MCC can be distinguished on the basis of the abundance of MCV; moreover, these subgroups differed in their expression of cancer related proteins, i.e. the Retinoblastoma protein (RB). The… Expand
Merkel cell polyomavirus detection in Merkel cell cancer tumors in Northern Germany using PCR and protein expression
Characterizing the presence of MCPyV sequences and viral early gene expression in a cohort of MCC cases selected in Northern Germany and suggesting that detection of M CPyV in Merkel cell carcinoma by PCR should be undertaken using multiple primer pairs are suggested. Expand
Retinoblastoma gene mutations detected by whole exome sequencing of Merkel cell carcinoma
This novel finding suggests that the retinoblastoma pathway dysregulation leads to an overlapping Merkel cell carcinoma phenotype and that oncogenesis occurs through either a polyomavirus-dependent (viral large T antigen expression) or polyomvirus-independent (host somatic mutation) mechanism. Expand
Merkel cell polyomavirus positive merkel cell carcinoma -- from diagnosis to therapy
This dissertation describes how the identification of a new viral cause of MCC was harnessed to develop new diagnostic assays and therapeutic options for MCC, including a monoclonal antibody that specifically recognizes both endogenous and transfected MCV large T antigen. Expand
Association of Merkel cell polyomavirus infection with clinicopathological differences in Merkel cell carcinoma.
The results suggest that Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas likely develop through different tumorigenic pathways and that the presence or absence of Merkelcell polyomvirus in the tumor is still an important factor that affects survival in patients with Merkel cell cancer. Expand
Bcl-2 expression indicates better prognosis of Merkel cell carcinoma regardless of the presence of Merkel cell polyomavirus
Bcl-2 positivity indicates better clinical stage at the time of diagnosis and a longer survival in MCC, and the recently found Merkel cell polyomavirus integrates clonally in the tumour genome, which suggests an important role in the pathogenesis of the disease. Expand
Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirus.
The results indicate that MCPyV is present in MCC tumors more frequently than previously reported and that mutations in TP53 tend to occur in M CC tumors that fail to express M CPyV large T antigen. Expand
Involvement of Merkel Cell Polyomavirus in the Etiology and Pathogenesis of Merkel Cell Carcinoma: A Systematic Review
A systematic review was developed to gather and evidence information about the involvement of MCV infection in the development of MCC, and results pointing to the MCV potential carcinogenic, infection, transmission and replication mechanisms, or even possible disease markers or therapeutic evaluations were found. Expand
RB1 gene in Merkel cell carcinoma: hypermethylation in all tumors and concurrent heterozygous deletions in the polyomavirus‐negative subgroup
The frequent heterozygous losses of the RB1 locus could partly explain the decreased RB expression in MCV‐negative MCC tumors, although the effects of RB1 mutations, coinciding promoter hypermethylation and, for example, miRNA regulation, cannot be excluded. Expand
Recent advances in the biology of Merkel cell carcinoma.
This review summarizes the advances in the molecular biology of Merkel cell carcinoma based on recent study results and suggests that increasing evidence strongly suggests that this virus is causally related to the development of Merkelcell carcinoma. Expand
Immunological detection of viral large T antigen identifies a subset of Merkel cell carcinoma tumors with higher viral abundance and better clinical outcome
Classic MCC viral oncogenesis characterized by abundance of MCPyV is clinically relevant as suggested by Sihto et al,16 who demonstrated that viral abundance in MCC correlates with survival. Expand


Merkel cell carcinoma subgroups by Merkel cell polyomavirus DNA relative abundance and oncogene expression
Data suggest that MCC may arise through different oncogenic pathways, including ones independent of pRb and MCPyV, and higher viral abundance tumors tended to be associated with less p53 expression, younger age at diagnosis and longer survival. Expand
T antigen mutations are a human tumor-specific signature for Merkel cell polyomavirus
It is shown that tumor-derived virus mutations do not affect retinoblastoma tumor suppressor protein (Rb) binding by LT but do eliminate viral DNA replication capacity, suggesting that MCV-positive MCC tumor cells undergo selection for LT mutations to prevent autoactivation of integrated virus replication that would be detrimental to cell survival. Expand
Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors
A monoclonal antibody is developed that specifically recognizes endogenous and transfected MCV large T (LT) antigen and expression of this putative viral oncoprotein in tumor cells provides the mechanistic underpinning supporting the notion that MCV causes a subset of MCC. Expand
Merkel cell polyomavirus is more frequently present in North American than Australian Merkel cell carcinoma tumors.
TO THE EDITOR Merkel cell carcinoma (MCC) is an increasingly common neuroendocrine cancer of the skin. MCC is an aggressive malignancy that is a significant cause of non-melanoma skin cancerExpand
The retinoblastoma susceptibility gene product undergoes cell cycle-dependent dephosphorylation and binding to and release from SV40 large T
Following a discrete population of these two proteins through the cell cycle, complex formation between T and RB may be regulated in part by thecell cycle-dependent phosphorylation and dephosphorylation of RB and by the quaternary structure of T. Expand
Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma
MC polyomavirus is frequently present in Merkel cell carcinoma of European patients.
The retinoblastoma susceptibility gene product undergoes cell cycledependent dephosphorylation and binding to and release from SV40 large T. Cell 1990;60:387–396
  • 1990
cycle - dependent dephosphorylation and binding to and release from SV 40 large T
  • 1990