Systematic Analysis of Human Oncogenic Viruses in Colon Cancer Revealed EBV Latency in Lymphoid Infiltrates

Overview

Journal Infect Agent Cancer

Publisher Biomed Central

Specialty Infectious Diseases

Date 2014 Jun 18

PMID 24936208

Citations 25

Authors

Loretta Fiorina

Mattia Ricotti

Alessandro Vanoli

Ombretta Luinetti

Elena Dallera

Roberta Riboni

Stefania Paolucci

Silvia Brugnatelli

Marco Paulli

Paolo Pedrazzoli

Fausto Baldanti

Vittorio Perfetti

Affiliations

Soon will be listed here.

Abstract

Background: Environmental factors may play a role in colon cancer. In this view, several studies investigated tumor samples for the presence of various viral DNA with conflicting results.

Findings: We undertook a systematic DNA analysis of 44 consecutive, prospectively collected primary tumor samples by real time and qualitative PCR for viruses of known or potential oncogenic role in humans, including polyomavirus (JCV, BKV, Merkel cell polyomavirus), HPV, HTLV, HHV-8 and EBV. Negative controls consisted of surgical resection margins. No evidence of genomic DNA fragments from tested virus were detected, except for EBV, which was found in a significant portion of tumors (23/44, 52%). Real-time PCR showed that EBV DNA was present at a highly variable content (median 258 copies in 10(5) cells, range 15-4837). Presence of EBV DNA had a trend to be associated with high lymphocyte infiltration (p = 0.06, χ2 test), and in situ hybridization with EBER1-2 probes revealed latency in a fraction of these lymphoid cells, with just a few scattered plasma cells positive for BZLF-1, an immediate early protein expressed during lytic replication. LMP-1 expression was undetectable by immunohistochemistry.

Conclusions: These results argue against a significant involvement of the tested oncogenic viruses in established colon cancer.

Citing Articles

Association of G12D mutation in the KRAS gene with HPV and EBV in gastrointestinal cancer tissues.

Hamidi Sofiani V, Ebrahimian Shiadeh A, Tabarraei A, Nikoo H, Sadeghi F, Kamrani G J Int Med Res. 2024; 52(12):3000605241302302.

PMID: 39673361 PMC: 11645758. DOI: 10.1177/03000605241302302.

Epstein-Barr Virus and Human Papillomavirus Coinfection in Colorectal Carcinoma: Systematic Review and Meta-Analysis of the Prevalence.

Banko A, Lazarevic I, Miljanovic D, Cupic M, Cirkovic A Microorganisms. 2024; 12(11).

PMID: 39597507 PMC: 11596815. DOI: 10.3390/microorganisms12112117.

Case-control study: Unveiling human polyomaviruses and papillomavirus in Egyptian colorectal cancer patients.

Darwish M, Allayeh A, Ahmed A, Abdelmaksoud M, Alkhalil S, Hakami M PLoS One. 2024; 19(6):e0304147.

PMID: 38861564 PMC: 11166297. DOI: 10.1371/journal.pone.0304147.

Incidence and association of high-risk HPVs and EBV in patients with advanced stages of colorectal cancer from Qatar.

Fernandes Q, Gupta I, Murshed K, Abo Samra H, Al-Thawadi H, Vranic S Hum Vaccin Immunother. 2023; 19(2):2220626.

PMID: 37293893 PMC: 10332205. DOI: 10.1080/21645515.2023.2220626.

Gut microbiota, an emergent target to shape the efficiency of cancer therapy.

Kouidhi S, Zidi O, Belkhiria Z, Rais H, Ayadi A, Ben Ayed F Explor Target Antitumor Ther. 2023; 4(2):240-265.

PMID: 37205307 PMC: 10185446. DOI: 10.37349/etat.2023.00132.

References

Baldanti F, Gatti M, Furione M, Paolucci S, Tinelli C, Comoli P . Kinetics of Epstein-Barr virus DNA load in different blood compartments of pediatric recipients of T-cell-depleted HLA-haploidentical stem cell transplantation. J Clin Microbiol. 2008; 46(11):3672-7. PMC: 2576592. DOI: 10.1128/JCM.00913-08. View

Moens B, Lopez G, Adaui V, Gonzalez E, Kerremans L, Clark D . Development and validation of a multiplex real-time PCR assay for simultaneous genotyping and human T-lymphotropic virus type 1, 2, and 3 proviral load determination. J Clin Microbiol. 2009; 47(11):3682-91. PMC: 2772591. DOI: 10.1128/JCM.00781-09. View

Bergonzini V, Salata C, Calistri A, Parolin C, Palu G . View and review on viral oncology research. Infect Agent Cancer. 2010; 5:11. PMC: 2881002. DOI: 10.1186/1750-9378-5-11. View

Wong N, Herbst H, Herrmann K, Kirchner T, Krajewski A, Moorghen M . Epstein-Barr virus infection in colorectal neoplasms associated with inflammatory bowel disease: detection of the virus in lymphomas but not in adenocarcinomas. J Pathol. 2003; 201(2):312-8. DOI: 10.1002/path.1442. View

Watzinger F, Suda M, Preuner S, Baumgartinger R, Ebner K, Baskova L . Real-time quantitative PCR assays for detection and monitoring of pathogenic human viruses in immunosuppressed pediatric patients. J Clin Microbiol. 2004; 42(11):5189-98. PMC: 525141. DOI: 10.1128/JCM.42.11.5189-5198.2004. View

Qu W, Jiang G, Cruz Y, Chang C, Ho G, Klein R . PCR detection of human papillomavirus: comparison between MY09/MY11 and GP5+/GP6+ primer systems. J Clin Microbiol. 1997; 35(6):1304-10. PMC: 229739. DOI: 10.1128/jcm.35.6.1304-1310.1997. View

Militello V, Trevisan M, Squarzon L, Biasolo M, Rugge M, Militello C . Investigation on the presence of polyomavirus, herpesvirus, and papillomavirus sequences in colorectal neoplasms and their association with cancer. Int J Cancer. 2009; 124(10):2501-3. DOI: 10.1002/ijc.24224. View

Saundh B, Tibble S, Baker R, Sasnauskas K, Harris M, Hale A . Different patterns of BK and JC polyomavirus reactivation following renal transplantation. J Clin Pathol. 2010; 63(8):714-8. DOI: 10.1136/jcp.2009.074864. View

Newcomb P, Bush A, Stoner G, Lampe J, Potter J, Bigler J . No evidence of an association of JC virus and colon neoplasia. Cancer Epidemiol Biomarkers Prev. 2004; 13(4):662-6. View

10.

Liu H, Ding Y, Li X, Yao K . Investigation of Epstein-Barr virus in Chinese colorectal tumors. World J Gastroenterol. 2003; 9(11):2464-8. PMC: 4656521. DOI: 10.3748/wjg.v9.i11.2464. View

11.

Theodoropoulos G, Panoussopoulos D, Papaconstantinou I, Gazouli M, Perdiki M, Bramis J . Assessment of JC polyoma virus in colon neoplasms. Dis Colon Rectum. 2005; 48(1):86-91. DOI: 10.1007/s10350-004-0737-2. View

12.

Pancaldi C, Corazzari V, Maniero S, Mazzoni E, Comar M, Martini F . Merkel cell polyomavirus DNA sequences in the buffy coats of healthy blood donors. Blood. 2011; 117(26):7099-101. DOI: 10.1182/blood-2010-09-310557. View

13.

Travaglione S, Fabbri A, Fiorentini C . The Rho-activating CNF1 toxin from pathogenic E. coli: a risk factor for human cancer development?. Infect Agent Cancer. 2008; 3:4. PMC: 2323363. DOI: 10.1186/1750-9378-3-4. View

14.

Laghi L, Randolph A, Chauhan D, Marra G, Major E, Neel J . JC virus DNA is present in the mucosa of the human colon and in colorectal cancers. Proc Natl Acad Sci U S A. 1999; 96(13):7484-9. PMC: 22112. DOI: 10.1073/pnas.96.13.7484. View

15.

Perfetti V, Ricotti M, Buonaguro F, Tirelli U, Pedrazzoli P . An overview of viral oncology in Italy - report from the Pavia meeting on solid tumors. Infect Agent Cancer. 2012; 7(1):23. PMC: 3523043. DOI: 10.1186/1750-9378-7-23. View

16.

van Engeland M, Derks S, Smits K, Meijer G, Herman J . Colorectal cancer epigenetics: complex simplicity. J Clin Oncol. 2011; 29(10):1382-91. DOI: 10.1200/JCO.2010.28.2319. View

17.

de Martel C, Ferlay J, Franceschi S, Vignat J, Bray F, Forman D . Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol. 2012; 13(6):607-15. DOI: 10.1016/S1470-2045(12)70137-7. View

18.

Grady W, Carethers J . Genomic and epigenetic instability in colorectal cancer pathogenesis. Gastroenterology. 2008; 135(4):1079-99. PMC: 2866182. DOI: 10.1053/j.gastro.2008.07.076. View

19.

Chiaravalli A, Longhi E, Vigetti D, De Stefano F, Deleonibus S, Capella C . Gastrointestinal cancers reactive for the PAb416 antibody against JCV/SV40 T-Ag lack JCV DNA sequences while showing a distinctive pathologic profile. J Clin Pathol. 2012; 66(1):44-9. DOI: 10.1136/jclinpath-2012-200963. View

20.

Hasan N, Pollack A, Cho I . Infectious causes of colorectal cancer. Infect Dis Clin North Am. 2010; 24(4):1019-39, x. DOI: 10.1016/j.idc.2010.07.009. View