PMID- 1361372 OWN - NLM STAT- MEDLINE DCOM- 19930125 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 80 IP - 12 DP - 1992 Dec 15 TI - Structural and functional analysis of oncogenes and tumor suppressor genes in adult T-cell leukemia/lymphoma shows frequent p53 mutations. PG - 3205-16 AB - The human T-cell lymphotropic virus type I (HTLV-I) is capable of inducing adult T-cell leukemia/lymphoma (ATLL). However, the long latency period between infection and development of ATLL, as well as the small fraction of the infected population that actually develops this disease, suggest that additional factors are involved in its pathogenesis. Therefore, we performed a molecular analysis of 10 cases of ATLL presenting in a nonendemic area that were shown to have HTLV-I sequences by polymerase chain reaction as well as clonal T-cell receptor beta gene rearrangements. We analyzed these cases for alterations in some of the oncogenes and tumor suppressor genes frequently involved in hematopoietic neoplasia. Specifically, we used a single-strand conformation polymorphism assay to determine the presence of mutations in the p53 tumor suppressor gene, as well as the K-RAS, N-RAS, H-RAS, and c-myc oncogenes. In addition, we studied the c-myc gene for rearrangements by Southern blotting and assessed expression of the retinoblastoma (Rb) and p53 genes by immunostaining. Analysis of the c-myc gene and the RAS family of oncogenes did not show any alterations. Also, the Rb gene was expressed in all cases analyzed. However, we found mutations of the p53 gene in 3 of the 10 cases and these results were confirmed by sequence analysis. In two of these cases, we showed by restriction fragment length polymorphism analysis of chromosome 17p sequences that the p53 mutations were accompanied by a loss of heterozygocity. Also, these mutations correlated with an altered pattern of p53 expression. Thus, mutations in the p53 locus may be a cofactor for the development of ATLL in some cases, whereas the c-myc, Rb, and RAS genes do not appear to be involved in these neoplasms. FAU - Cesarman, E AU - Cesarman E AD - Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, NY. FAU - Chadburn, A AU - Chadburn A FAU - Inghirami, G AU - Inghirami G FAU - Gaidano, G AU - Gaidano G FAU - Knowles, D M AU - Knowles DM LA - eng GR - CA48236/CA/NCI NIH HHS/United States GR - EY06337/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (DNA, Neoplasm) RN - 0 (DNA, Viral) RN - 0 (Oligodeoxyribonucleotides) RN - 0 (Tumor Suppressor Protein p53) SB - IM GS - H-RAS GS - K-RAS GS - Ki-67 GS - N-RAS GS - RAS GS - Rb GS - c-myc GS - p53 MH - Alleles MH - Base Sequence MH - Blotting, Southern MH - Bone Marrow/pathology MH - Cloning, Molecular MH - DNA, Neoplasm/genetics/isolation & purification MH - DNA, Viral/genetics/isolation & purification MH - Exons MH - Gene Rearrangement MH - Gene Rearrangement, beta-Chain T-Cell Antigen Receptor MH - Genes, Retinoblastoma MH - *Genes, Tumor Suppressor MH - Genes, myc MH - *Genes, p53 MH - Genes, ras MH - Genotype MH - Human T-lymphotropic virus 1/genetics/*isolation & purification MH - Humans MH - Leukemia, T-Cell/blood/*genetics/immunology/pathology MH - Leukemia-Lymphoma, Adult T-Cell/blood/*genetics/immunology/pathology MH - Molecular Sequence Data MH - *Mutation MH - Oligodeoxyribonucleotides MH - *Oncogenes MH - Polymerase Chain Reaction MH - Polymorphism, Restriction Fragment Length MH - Restriction Mapping MH - Tumor Suppressor Protein p53/analysis/genetics EDAT- 1992/12/15 00:00 MHDA- 1992/12/15 00:01 CRDT- 1992/12/15 00:00 PHST- 1992/12/15 00:00 [pubmed] PHST- 1992/12/15 00:01 [medline] PHST- 1992/12/15 00:00 [entrez] AID - S0006-4971(20)85922-9 [pii] PST - ppublish SO - Blood. 1992 Dec 15;80(12):3205-16.