title: Alterations in telomeric repeat length in lung cancer are associated with loss of heterozygosity in p53 and Rb.
abstract: In the two-stage model of controlling cellular senescence in cultured human fibroblasts, retinoblastoma (Rb) and p53 proteins may be key factors regulating the mortality stage 1 mechanism. In addition, the critical loss of telomeric DNA due to the end-replication problem may result in the mortality stage 2 mechanism. Cells which acquire telomerase activity can overcome the M2 mechanism by stabilizing telomere length and thus become immortal (telomere hypothesis). At present it is known whether cellular immortality is a prerequisite for all human cancers. To investigate this question and the applicability of the two-stage model to human cancers, we analysed the relationship between alterations of telomere length and other genetic changes in lung cancer. Among 60 primary lung cancer tissues, telomere length alterations were observed in 16 tumors (26.7%) including 14 with short and two with elongated telomeres. Ten of them revealed allelic loss of both p53 and Rb genes, and remaining six showed no abnormalities in both genes. We propose that inactivation of both p53 and Rb genes may promote cell divisions causing telomere shortening in lung cancer as in the two-stage model, while there may be another pathway to overcome both M1 and M2 mechanisms, especially for adenocarcinoma.
authors.affiliation: Second Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hiyama
authors.forename: S
authors.initials: S
authors.lastname: Ishioka
authors.forename: Y
authors.initials: Y
authors.lastname: Shirotani
authors.forename: K
authors.initials: K
authors.lastname: Inai
authors.forename: E
authors.initials: E
authors.lastname: Hiyama
authors.forename: I
authors.initials: I
authors.lastname: Murakami
authors.forename: T
authors.initials: T
authors.lastname: Isobe
authors.forename: T
authors.initials: T
authors.lastname: Inamizu
authors.forename: M
authors.initials: M
authors.lastname: Yamakido
mesh_terms: D001483:Base Sequence; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D016161:Genes, Retinoblastoma; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D016615:Telomere