Abstract
The data presented here indicate that the pathogenesis of AIDS-NHL is variably associated with multiple genetic alterations including monoclonal EBV infection, oncogene activation (c-myc, N-, Ki-ras) and tumor suppressor gene (p53) inactivation. Up to three (3 cases) or four (1 case) different lesions have been observed in the same tumor. The distribution of these lesions among the various histotypes is heterogeneous, although some preferential associations have been found either between lesion and histotype or between lesions. The most notable case involves p53 mutations/loss that is exclusively associated with the SNCC lymphoma subtype. Since alterations of the c-myc gene occur at very high frequency in this same histiotype it is possible that both lesions may be required for the pathogenesis of the BL phenotype. The consistent negativity of p53 lesions in other NHLs associated or non associated with HIV infection reinforces this hypothesis. Finally, we note that the frequency of p53 mutations is significantly higher in AIDS-BL than in non HIV-related BL, although the significancy of this difference remains to be assessed. This study confirms the relatively low frequency of EBV infection in systemic AIDS-NHL in general, but reinforces the notion that EBV may be required for the pathogenesis of AIDS-LC-IBP, as recently suggested by the high frequency of EBV positivity in primary CNS AIDS-NHL which are mostly represented by LC-IBP. Conversely, the low frequency of EBV sequences in the AIDS-SNCC lymphomas appears similar to that observed in sBL. Only in a small minority of cases were ras oncogene mutations found, mostly associated with the BL type. Since ras mutations have never been found in non HIV-related NHL, we examined whether these mutations could be related to the potential mutagenic action of antiretroviral agents, namely AZT. However, none of the patients included in our survey had received previous antiviral therapy. The presence of multiple lesions in some AIDS-NHL is perhaps suprising considering the relatively short time involved in the development of these tumors (4-5 years), and the fact that, since only a few common lesions have been studied, additional presently unknown alterations are likely to be present. While numerous studies have defined the multistep nature of tumorigenesis, the example of the multi-lesion pathogenesis of colon carcinoma has been taken to suggest that the long time (30-40 years) involved in tumor development is related to the number of independent genetic steps/lesions required. However, the example of some cases of AIDS-NHL suggests that genetic lesions may accumulate more rapidily at least in some tissues.
Lingua originale | Inglese |
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pagine (da-a) | 731-735 |
Numero di pagine | 5 |
Rivista | AIDS Research and Human Retroviruses |
Volume | 8 |
Numero di pubblicazione | 5 |
Stato di pubblicazione | Pubblicato - 1992 |
Pubblicato esternamente | Sì |