Chromosome 3p21.3 region is frequently (>90%) deleted in lung and other major human carcinomas. We subdivided 3p21.3 into LUCA and AP20 subregions and discovered frequent homozygous deletions (10 -18%) in both subregions. This finding strongly implies that they harbor multiple tumor suppressor genes involved in the origin and͞or development of major epithelial cancers. In this study, we performed an initial analysis of RBSP3͞HYA22, a candidate tumor suppressor genes located in the AP20 region. Two sequence splice variants of RBSP3͞HYA22 (A and B) were identified, and we provide evidence for their tumor suppressor function. By sequence analysis RBSP3͞HYA22 belongs to a gene family of small C-terminal domain phosphatases that may control the RNA polymerase II transcription machinery. Expression of the gene was drastically (>20-fold) decreased in 11 of 12 analyzed carcinoma cell lines and in three of eight tumor biopsies. We report missense and nonsense mutations in tumors where RBSP3͞HYA22 was expressed, growth suppression with regulated transgenes in culture, suppression of tumor formation in severe combined immunodeficient mice, and dephosphorylation of ppRB by RBSP3͞HYA22, presumably leading to a block of the cell cycle at the G1͞S boundary.

We report the molecular characterization, with subtyping of both K1 and K14.1/K15 genomic regions, of seven new human herpesvirus-8 (HHV-8) strains from Russian patients with classical Kaposi's sarcoma. Phylogenetic studies, based on the complete K1 gene/protein analysis, indicate that six of these strains belong to the A subtype, with one belonging to the A4 group and exhibiting a unique deletion of 19 amino acids in the VR2 region at position 186-204. PCR-based studies of the K14.1/K15 genomic region indicate that four of the new strains were of the M subtype while three belonged to the P subtype. Our study indicates an important genetic diversity of the HHV-8 strains currently present in Russia, including a new peculiar strain possessing a unique deletion in the VR2 segment, and confirms the absence of correlation between the K1 and K14.1/K15 molecular subtypes, as M and P genotypes can be observed in the A K1 subtype.

We report the molecular characterization of 38 new Kaposi's sarcoma-associated herpesvirus (KSHV) strains from Russian patients with either classic (25 cases), epidemic/AIDS-associated (7 cases), or posttransplant/immunosuppressed patients (6 cases), or Kaposi's sarcoma (KS). While a complete sequence of the K1 gene (870 bp) was obtained from 30 strains, only partial sequences of the hypervariable regions VR1 (372 bp) and/or VR2 (381 bp) of the K1 gene were obtained from eight strains of KS paraffin blocks. Sequence comparison and phylogenetic studies indicate that the novel KSHV strains belong to either the A subtype (28 cases) or the C subtype (10 cases). Within the 28 strains of A subtype, 24 (86%) belong to the large A' subgroup, mostly A1 and A1' clades, and 4 belong to the A" subgroup, mostly A3 clade. Within the 10 strains of subtype C, 4 were of C' subgroup, and 6 of the C". Some molecular variants of subtype A' were observed, with 3 strains exhibiting an insertion of a single amino acid at the position 65 and 2 strains (both from AIDS-KS) with an unique deletion of 17 amino acids in the VR2 region. Polymerase chain reaction-based subtyping of the K14.1 genomic region indicated that most (23/32) of the novel strains belonged to the P subtype. The results indicate that despite a wide genetic diversity of A and C K1 subtypes of KSHV strains present in Russia, most are closely related and belong to the A1 or A1' molecular clades suggesting a common origin. This study also expands the data regarding the absence of any correlation between a K1 molecular subtype and a specific KS type (classic, epidemic, or posttransplant), as well as between the K1 and K14.1 molecular subtypes.