Cytomegalovirus Infection Leads to Pleomorphic Rhabdomyosarcomas in Trp53+/-Mice

• Published in: Cancer research (Chicago, Ill.) Vol. 72; no. 22; pp. 5669 - 5674
• Main Authors: PRICE, Richard L, BINGMER, Katherine, HARKINS, Lualhati, IWENOFU, O. Hans, KWON, Chang-Hyuk, COOK, Charles, PELLOSKI, Christopher, ANTONIO CHIOCCA, E
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.11.2012
• Subjects: Animals; Antigens, Viral - biosynthesis; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Cytomegalovirus - genetics; Cytomegalovirus - immunology; Cytomegalovirus - isolation & purification; Cytomegalovirus Infections - genetics; Cytomegalovirus Infections - metabolism; Cytomegalovirus Infections - pathology; DNA, Viral - analysis; Gene Expression; Medical sciences; Mice; Mice, Transgenic; Muscle Neoplasms - genetics; Muscle Neoplasms - metabolism; Muscle Neoplasms - virology; Neoplasms, Connective Tissue - genetics; Neoplasms, Connective Tissue - metabolism; Neoplasms, Connective Tissue - virology; Rhabdomyosarcoma - genetics; Rhabdomyosarcoma - metabolism; Rhabdomyosarcoma - virology; Tumor Suppressor Protein p53 - biosynthesis; Tumor Suppressor Protein p53 - genetics; Tumors; Viruses; Cytomegalovirus; Sarcoma; Murine cytomegalovirus; Herpesviridae; Rodentia; Tumorigenicity; Malignant tumor; Betaherpesvirinae; Infection; Virus; Striated muscle disease; Vertebrata; Mammalia; TP53 Gene; Mouse; Animal; Viral disease; Pleomorphic rhabdomyosarcoma; Mutation; Cancer
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-12-2425

Cytomegalovirus (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.