title: Integration of human T-cell leukemia virus type 1 in genes of leukemia cells of patients with adult T-cell leukemia.
abstract: Adult T-cell leukemia (ATL) occurs after a long latent period of persistent infection by human T-cell leukemia virus type 1 (HTLV-1). However, the mechanism of oncogenesis by HTLV-1 remains to be clarified. It was reported that the incidence curve of ATL versus age was consistent with a multistage carcinogenesis model. Although HTLV-1 is an oncogenic retrovirus, a mechanism of carcinogenesis in ATL by insertional mutagenesis as one step during multistage carcinogenesis has not been considered thus far, because the exact integration sites on the chromosome have not been analyzed. Here we determined the precise HTLV-1 integration sites on the human chromosome, by taking advantage of the recently available human genome database. We isolated 25 integration sites of HTLV-1 from 23 cases of ATL. Interestingly, 13 (52%) of the integration sites were within genes, a rate significantly higher than that expected in the case of random integration (P = 0.043, chi(2) test). These results suggest that preferential integration into genes at the first infection is a characteristic of HTLV-1. However considering that some of the genes are related to the regulation of cell growth, the integration of HTLV-1 into or near growth-related genes might contribute to the clonal selection of HTLV-1-infected cells during multistage carcinogenesis of ATL.
authors.affiliation: Department of Biochemistry and Molecular Oncology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8575, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Hanai
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nitta
authors.forename: Momoko
authors.initials: M
authors.lastname: Shoda
authors.forename: Masakazu
authors.initials: M
authors.lastname: Tanaka
authors.forename: Naomi
authors.initials: N
authors.lastname: Iso
authors.forename: Izuru
authors.initials: I
authors.lastname: Mizoguchi
authors.forename: Shinji
authors.initials: S
authors.lastname: Yashiki
authors.forename: Shunro
authors.initials: S
authors.lastname: Sonoda
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Toshiro
authors.initials: T
authors.lastname: Nagasawa
authors.forename: Masanao
authors.initials: M
authors.lastname: Miwa
mesh_terms: D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics / Q000648:ultrastructure; D004273:DNA, Neoplasm / Q000032:analysis*; D004279:DNA, Viral / Q000032:analysis*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000821:virology*; D011533:Proviruses / Q000235:genetics / Q000302:isolation & purification*; D016662:Virus Integration
chemical_list: D004273:DNA, Neoplasm; D004279:DNA, Viral