Heterogeneity of TT virus related sequences isolated from human tumour biopsy specimens

Abstract

TT viruses have recently been reported in serum samples from varying percentages of human blood donors and in patients with chronic liver disease. However, no association with human pathology has yet been reported. In a pilot study we analysed 162 biopsy specimens from various human cancers and from colon polyps for the presence of TT virus related sequences by polymerase chain reaction using three sets of nested primers for TT virus detection. All gels were subjected to Southern blot hybridisation, and DNA from hybridising bands was cloned and sequenced. A total of 54.3% of tumour specimens contained identifiable TT virus related sequences. Specimens from hypopharynx, larynx, endometrial, ovarian and bladder cancers were 14-35% positive and gastrointestinal cancers (oesophagus, stomach, colon, rectum) and colon polyps 57-100% positive. Lung cancers (68.4%), mammary cancers (50%), multiple myelomas (85.7%) and human leukaemias (53.3%) also revealed a high prevalence of TT virus related sequences. Since normal control tissues were not available for the tumour biopsy specimens tested, these data do not permit conclusions concerning a possible causal relationship between the virus infections and carcinogenesis. Another aspect, however, deserves attention: the heterogeneity of TT virus clones obtained from the specimens tested here was striking: 66 novel sequences, probably belonging to new types were identified. Only 16 clones corresponded by more than 97% of their sequences to established prototypes. Even individual tumours commonly contained sequences substantially diverging in nucleic acid composition. Up to five different types were identified within an individual tumour. The high variability of these virus types suggests that additional primer combinations within the highly conserved region of the genome would detect a still higher rate of positive tumours.