Viral Integration Analysis Reveals Likely Common Clonal Origin of Bilateral HPV16-Positive, p16-Positive Tonsil Tumors.

Autor:	Pinatti LM; Cancer Biology Program, Program in the Biomedical Sciences, Rackham Graduate School, University of Michigan, Ann Arbor, MI, USA.; Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA., Walline HM; Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA., Carey TE; Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA., Klussmann JP; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Huebbers CU; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.; Jean-Uhrmacher-Institute for Otorhinolaryngological Research, University of Cologne, Cologne, Germany.
Jazyk:	angličtina
Zdroj:	Archives of clinical and medical case reports [Arch Clin Med Case Rep] 2020; Vol. 4 (4), pp. 680-696. Date of Electronic Publication: 2020 Jul 13.
DOI:	10.26502/acmcr.96550248
Abstrakt:	Infections with high-risk human papilloma viruses (HPV) are responsible for a significant number of oropharyngeal squamous cell carcinoma (OPSCC), with infection rates currently rising at epidemic rates in the western world. Synchronous bilateral HPV+ tumors of both tonsils are a very rare event whose understanding, however, could provide important insights into virus-driven tumor development and progression and whether such integration events are of clonal origin. In this study we analyzed a single case of a bilateral tonsillar p16+ HPV+OPSCC. The viral integration status of the various tumor samples was determined by integration-specific PCR methods and sequencing, which identified viral insertion sites and affected host genes. Integration events were further confirmed by transcript analysis. Analysis of the tumors revealed common viral integration events involving the CD36 gene, as well as a unique event in the LAMA3 gene which resulted in loss of LAMA3 exon one in both tissues that had lost the complex viral LAMA3 integration event. In addition, there were several integration events into intergenic regions. This suggests a common origin but individual evolution of the tumors, supporting the single-clone hypothesis of bilateral tumor development. This hypothesis is further supported by the fact that the two cellular genes LAMA3 and CD36 as targets of viral integration are involved in cell migration and ECM-receptor interactions, which provides a possible mechanism for clonal migration from one tonsil to another. Competing Interests: Conflict of Interests The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.
Databáze:	MEDLINE
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