Candidate chromosomal regions for genes involved in activation of alternative lengthening of telomeres in human immortal cell lines.
Either telomerase or alternative mechanisms known as alternative lengthening of telomeres (ALT) are activated in human immortal cells to maintain or lengthen their telomeres. To screen candidate chromosomes harboring gene(s) involved in activation of the telomere maintenance mechanisms that are repressed in normal, mortal cells and lost in immortal cells, we examined loss of heterozygosity (LOH) on the 22 autosomes and the X chromosome in 22 in vitro established human immortal cell lines consisting of 9 telomerase-positive cell lines and 13 ALT-positive cell lines. For detecting LOH, PCR analysis was performed with 66 polymorphic microsatellite markers from candidate genomic regions previously implicated for putative human senescence genes, telomerase repressor genes, or tumor suppressor genes. LOH involving chromosome 8 was observed at 25 of 62 (40%) informative loci in 8 of 13 (61%) ALT-positive cell lines. Particularly, when assayed with D8S339 adjacent to the Werner's syndrome gene, LOH was found in 6 of 12 (50%) informative ALT-positive cell lines. In contrast, no LOH on chromosome 8 was detected at 41 informative loci in any of 9 telomerase-positive cell lines. No other chromosomes showed high frequencies of LOH common in either ALT-positive or telomerase-positive cell lines. Although further LOH analysis with additional markers remains to define the specific region on chromosome 8, our results suggest that gene(s) involved in activation of the ALT pathway in human immortal cell lines may localize on chromosome 8.
Shigeeda
Nobumasa
N
Oral and Maxillofacial Surgery, The Nippon Dental University Hospital at Tokyo, 102-8158, Tokyo, Japan.
Uchida
Minoru
M
Barrett
J Carl
JC
Tsutsui
Takeki
T
D002461:Cell Line, Transformed; D016922:Cellular Senescence / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics*
D019098:Telomerase