Presence and expression of the simian virus-40 genome in human giant cell tumors of bone

Our plain-English summary of Presence and expression of the simian virus-40 genome in human giant cell tumors of bone, by G. Gamberi, M.S. Benassi, F. Pompetti, et al (Genes, Chromosomes & Cancer, 2000).

The study

• Authors: G. Gamberi, M.S. Benassi, F. Pompetti, C. Ferrari, P. Ragazzini, M.R. Sollazzo, L. Molendini, M. Merli, G. Magagnoli, F. Chiesa, A.G. Gobbi, A. Powers, P. Picci
• Journal: Genes, Chromosomes & Cancer
• Published: 2000;28(1):23-30
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

SV40 DNA sequences have been found in human tumors, such as mesotheliomas, ependymomas, and bone tumors, suggesting that SV40 may be involved in their etiology. The FOS oncogene could play an important role in bone development because SV40 is able to induce FOS in cell culture. In this study, the presence of SV40 sequences, large T antigen (Tag), and FOS protein expression were investigated in 120 giant cell tumors (GCTs), moderately benign bone tumors that in some cases can progress to a malignant phenotype. Polymerase chain reaction (PCR), using primers that amplify the RB1 pocket binding domain and the intron of Tag, was used to analyze GCT for the presence of SV40 DNA. Tag and FOS protein expression was evaluated by immunohistochemistry. SV40 sequences were found in 30/107 GCTs, and of these, 22/30 samples expressed Tag protein (73%) and 15/30 overexpressed the FOS oncogene (50%). FOS was undetectable in 77 SV40-negative GCTs. Sequence analysis of the amplified DNAs confirmed that the amplified sequences corresponded to SV40 DNA. The correlation between FOS overexpression and SV40-positive GCTs was highly statistically significant (P < 0.001). These results show that SV40 DNA sequences and SV40 Tag are present in GCTs and might induce FOS activity. These data suggest that SV40 might play a role in the development and progression of some GCTs.

Copyright 2000 Wiley-Liss, Inc.

In plain English

This laboratory study, from the Rizzoli Institute in Bologna, Italy, looked for the monkey virus SV40 in giant cell tumors of bone, a usually benign bone tumor. It did not study asbestos or mesothelioma. Of 143 archived tumor specimens, 120 could be analyzed: 107 primary tumors and 13 lung metastases. The authors used PCR to detect viral DNA, confirmed by DNA sequencing. They also stained for the FOS protein and with an antibody recognizing both large T and small t viral antigens. SV40 DNA was found in 30 of 107 primary tumors. Of these 30, 22 (73%) showed T antigen staining and 15 showed strong FOS staining. The 77 SV40-negative tumors were negative for T antigen and negative to weak for FOS. FOS overexpression was reported as significantly more common in SV40-positive tumors. Three of 13 primary tumors that developed metastases contained SV40 and showed T antigen. No significant link was found between SV40 and disease-free survival, sex or birth year. The authors concluded that SV40 might contribute to the development and progression of these tumors. They noted that direct biochemical evidence for the proposed mechanism is still needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study of archived, formalin-fixed, paraffin-embedded tumor specimens using PCR, DNA sequencing and immunohistochemistry
• Who was studied: 120 giant cell tumor specimens (107 primary tumors and 13 lung metastases from these tumors), taken from 143 specimens selected for cellularity. The specimens came from patients referred to the Rizzoli Institute, Bologna, Italy, who were born from 1889 to 1977. Of the 107 primary tumors, 13 came from patients who later developed lung metastases and 94 from patients who remained disease-free.
• Exposure: Presence of simian virus 40 (SV40) DNA, detected by PCR using two primer sets that give 172 bp and 574 bp products. Immunohistochemistry measured SV40 antigen expression, using an antibody that recognizes both large T and small t antigen, and FOS protein expression. No asbestos exposure was studied.
• Main results:
  • SV40 DNA was found in 30 of 107 primary giant cell tumors; sequencing was reported to confirm that the amplified sequences were authentic SV40
  • 22 of the 30 SV40-positive tumors (73%) showed T antigen staining. The antibody used (Pab 108) recognizes both large T and small t antigen.
  • All 77 tumors negative for SV40 DNA were also negative for T antigen
  • 15 of the 30 SV40-positive tumors showed uniform, strong FOS staining in more than 50% of tumor cells; 6 more were moderately to weakly positive and 9 were FOS negative
  • The 77 SV40-negative tumors showed negative to weak FOS staining
  • FOS overexpression was significantly more common in the 30 SV40-positive tumors than in the 77 SV40-negative tumors (chi-square 37.6, P less than 0.001)
  • 3 of the 13 primary tumors that developed metastases (23%) contained SV40 and expressed T antigen; one lung metastasis contained SV40 and expressed T antigen
  • No significant correlation was found between SV40 and disease-free survival, sex, or year of birth
  • SV40 was found in 17/52 (33%) patients born 1946 to 1963, 6/37 (16%) born before 1945, and 7 of 18 (reported as 38%) born 1964 to 1977. The authors suggested the earlier groups may have received contaminated polio vaccines. They said the youngest group should not have, which suggests transmission by another route.
• The authors' conclusion: The authors concluded that their findings suggest SV40 might induce AP1 activity and contribute to giant cell tumor development and tumor progression
• Limitations the authors state:
  • Direct biochemical evidence is still needed to show that SV40 induces AP1 activity in giant cell tumor cells
  • In 8 tumors SV40 DNA was found without T antigen expression; the authors said this may or may not be biologically significant

Topics

Medical terms in this study, explained in our Lexicon: SV40, Mesothelioma, Etiology, Immunohistochemistry.

Related studies

• Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences — H.I. Pass, J.S. Donington, et al. (1998)
• The presence of simian-virus 40 sequences in mesothelioma and mesothelial cells is associated with high levels of vascular endothelial growth factor — P. Cacciotti, L. Strizzi, et al. (2002)
• Human T cell responses to endogenously presented HLA-A*0201 restricted peptides of Simian virus 40 large T antigen — M.P. Velders, M.F. Macedo, et al. (2001)
• Simian virus 40 infection down-regulates the expression of nitric oxide synthase in human mesothelial cells — E. Aldieri, S. Orecchia, et al. (2004)
• Evidence against a role for SV40 infection in human mesotheliomas and high risk of false-positive PCR results owing to presence of SV40 sequences in common laboratory plasmids — F. López-Ríos, P.B. Illei, et al. (2004)
• No implication of Simian virus 40 in pathogenesis of malignant pleural mesothelioma in Slovenia — J. Hmeljak, I. Kern, et al. (2010)

Browse more research in Genes, Chromosomes & Cancer, or return to medical research.