00085472can122425-sup-f2_600k.pdf (600.25 kB)
Supplementary Figure 2 from Cytomegalovirus Infection Leads to Pleomorphic Rhabdomyosarcomas in Trp53+/− Mice
journal contributionposted on 2023-03-30, 21:25 authored by Richard L. Price, Katherine Bingmer, Lualhati Harkins, O. Hans Iwenofu, Chang-Hyuk Kwon, Charles Cook, Christopher Pelloski, E. Antonio Chiocca
PDF file - 600K, Control IHC and additional HCMV IHC in human RMS
ARTICLE ABSTRACTCytomegalovirus (CMV) has been detected in several human cancers, but it has not proven to be oncogenic. However, recent studies have suggested mechanisms through which cytomegalovirus may modulate the tumor environment, encouraging its study as a positive modifier of tumorigenesis. In this study, we investigated the effects of cytomegalovirus infection in Trp53 heterozygous mice. Animals were infected with murine cytomegalovirus (MCMV) after birth at 2 days (P2) or 4 weeks of age and then monitored for tumor formation. Mice injected at 2 days of age developed tumors at a high frequency (43%) by 9 months of age. In contrast, only 3% of mock-infected or mice infected at 4 weeks developed tumors. The majority of tumors from P2 MCMV–infected mice were pleomorphic rhabdomyosarcomas (RMS) harboring MCMV DNA, RNA, and protein. An examination of clinical cases revealed that human RMS (embryonal, alveolar, and pleomorphic) harbored human cytomegalovirus IE1 and pp65 protein as well as viral RNA. Taken together, our findings offer support for the hypothesis that cytomegalovirus contributes to the development of pleomorphic RMS in the context of Trp53 mutation, a situation that occurs with high frequency in human RMS. Cancer Res; 72(22); 5669–74. ©2012 AACR.
CarcinogenesisTumor initiation and promotionOncogenes & Tumor Suppressorsp53Pediatric CancersPreclinical ModelsAnimal models of cancerProgression, Invasion & MetastasisTumor progressionSarcomasSoft-tissue sarcomaStem Cell BiologyViral OncogenesisDNA tumor virusesHost-virus interactionsHuman tumor virusesViral transformation and carcinogenesis