We have applied a functional test for tumour antagonizing genes based on human chromosome 3 (chr3)–mouse fibrosarcoma A9 MCHs that were studied in vitro and after growth as tumours in severe combined immunodeficiency (SCID) mice. Previously, we reported that 9 out of the 36 SCID‐tumours maintained the transferred chr3 (“chr3+” tumours), but lost the expression of the known human TSG fragile histidine triad gene (FHIT) in contrast to 14 other 3p‐genes examined. Here we report the results of the duplex RT‐PCR analysis of 9 “chr3+” tumours and 3 parental MCHs. We have examined the expression of 34 human 3p‐genes from known cancer‐related regions of instability, including 13 genes from CER1 defined by us previously at 3p21.33–p21.31 and 10 genes from the LUCA region at 3p21.31. We have found that in addition to FHIT, expression of the LTF gene from CER1 at 3p21.33‐p21.31 was lost in all 9 tumours analyzed. The transcript of the solute carrier family 38 member 3 gene (SLC38A3) gene from LUCA region at 3p21.31 was not found in 8 and was greatly reduced in 1 out of these 9 tumours. Expression of the down‐regulated in renal cell carcinoma gene (DRR1) gene at 3p14.2 was lost in 7 and down regulated in 2 “chr3+” tumours. In the SCID‐tumour derived cell lines treatment with 5‐aza‐2′‐deoxycytidine restored the mRNA expression of LTF, indicating the integrity of DNA sequences. Notably that transcription of the LTF and 2 flanking genes, LRRC2 and TMEM7, as well as transcription of the SLC38A3 gene, were also impaired in all 5 RCC cell lines analyzed. Our data indicate these genes as putative tumour suppressor genes.
Peripheral blood mononuclear cells and plasma of 113 patients with neurological disorders and 150 blood donors were analyzed for HHV-6 and HHV-7 sequences by PCR. The prevalence of HHV-6 was significantly higher in patients with multiple sclerosis (P < 0.01) than in cases of nondemyelinating diseases of the central and demyelinating diseases of the peripheral nervous systems and blood donors. HHV-6 viremia was found only in patients with multiple sclerosis, predominantly in the active phase of the disease. A significantly higher frequency of HHV-7 reactivation in patients with demyelinating diseases of the peripheral nervous system suggests also its association with demyelinating processes.
A recently described sequence from a probable 5th human exogenous retrovirus, HRV‐5, is related to type A, B and D retroviruses. It was initially detected in a salivary gland biopsy from a patient with Sjögren's syndrome, but it is not consistently associated with this disease. We searched for the HRV‐5 sequence in DNA extracted from whole blood of 300 blood donors, 81 patients with hematological malignancy and 21 patients with neurological disease using PCR. While samples from none of the blood donors and the neurological patients became positive, 3 of the 81 patients with hematological malignancy were HRV‐5 DNA positive. All 3 had B‐cell non‐Hodgkin's lymphoma of low grade. The difference in frequency between NHL and controls is statistically significant. HRV‐5 DNA was found in DNA from whole blood and in plastic‐adherent cells but not in tumor cell DNA. Thus, monocytes/macrophages may be preferred targets for HRV‐5. Our result, together with a previous finding of HRV‐5 DNA in 2 NHL cases, is compatible with an association between HRV‐5 and NHL, whether causal or not. Int. J. Cancer 85:762–770, 2000.