Different simian virus 40 genomic regions and sequences homologous with SV40 large T antigen in DNA of human brain and bone tumors and of leukocytes from blood donors.
BACKGROUND
Many studies found only a small fragment of the large T-antigen coding sequences in human tumors, raising doubts on authenticity of SV40 sequences detected in these samples.


METHODS
Five different regions of SV40 DNA were investigated in 106 fresh human tumor biopsies (25 brain, 69 bone, 12 Wilms' tumors), 71 tumor-derived cell cultures (38 from brain and 33 from bone tumors) and normal tissues (5 fresh bone biopsies and 38 buffy coats) by polymerase chain reaction (PCR) techniques and filter hybridization with specific oligoprobes. Expression of SV40 Tag sequences was analyzed in human tumor specimens by RT-PCR.


RESULTS
SV40 large T-antigen sequences were detected at high prevalence, in human biopsies of primary brain (37-44%) and bone (21-37%) tumors, in cell cultures derived from brain (30-54%) and bone (53-80%) tumors. SV40 Tag sequences were detected in 29% of buffy coats of blood donors. However, only four brain tumor cell lines showed all the five regions of the SV40 genome investigated. Expression of SV40 Tag sequences was found in 11 of 27 (41%) human tumor samples. DNA sequence analysis indicated that the PCR-amplified products belong to the SV40 wild type. Polymerase chain reaction products of Tag middle portion from 20 of 78 (26%) samples showed a 97% homology with telomeric sequences of human chromosomes 10 and 11.


CONCLUSIONS
Authentic SV40 sequences were detected in human samples. The expression of SV40 Tag sequences indicates that SV40 could play a role, as a cofactor, in the onset/progression of specific human cancers. The inability to detect some regions of the virus genome may suggest that those regions are not required for tumor persistence or growth and have been lost or, alternatively, may be the result of assay conditions that were unable to PCR-amplify those regions in the tumors.
Martini
Fernanda
F
Department of Morphology and Embryology, Section of Histology and Embryology, University of Ferrara, Ferrara, Italy.
Lazzarin
Lorena
L
Iaccheri
Laura
L
Vignocchi
Beatrice
B
Finocchiaro
Gaetano
G
Magnani
Ivana
I
Serra
Massimo
M
Scotlandi
Katia
K
Barbanti-Brodano
Giuseppe
G
Tognon
Mauro
M
D000952:Antigens, Polyomavirus Transforming / Q000032:analysis / Q000235:genetics*; D001782:Blood Donors; D001859:Bone Neoplasms / Q000235:genetics* / Q000821:virology*; D001932:Brain Neoplasms / Q000235:genetics* / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D006801:Humans; D007962:Leukocytes / Q000821:virology; D009841:Oligonucleotides; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D013539:Simian virus 40 / Q000235:genetics*
D000952:Antigens, Polyomavirus Transforming; D004279:DNA, Viral; D009841:Oligonucleotides