Telomerase activity in gastric cancer.
Although many genetic alterations have been reported in gastric cancer, it is not known whether all gastric tumors are capable of indefinite proliferative potential, e.g., immortality. The expression of telomerase and stabilization of telomeres are concomitant with the attainment of immortality in tumor cells; thus, the measurement of telomerase activity in clinically obtained tumor samples may provide important information useful both as a diagnostic marker to detect immortal cancer cells in clinical materials and as a prognostic indicator of patient outcome. Telomerase activity was analyzed in 66 primary gastric cancers with the use of a PCR-based assay. The majority of tumors (85%) displayed telomerase activity, but telomerase was undetectable in 10 tumors (15%), 8 of which were early stage tumors. Most of the tumors with telomerase activity were large and of advanced stages, including metastases. Survival rate of patients of tumors with detectable telomerase activity was significantly shorter than that of those without telomerase activity. Alterations of telomere length (reduced/elongated terminal restriction fragments) were detected in 14 of 66 (21%) gastric cancers, and all 14 had telomerase activity. Cellular DNA contents revealed that all 22 aneuploid tumors had detectable telomerase activity. The present results indicate that telomerase activation may be required as a critical step in the multigenetic process of tumorigenesis, and that telomerase is frequently but not always activated as a late event in gastric cancer progression.
Hiyama
E
E
Department of General Medicine, Hiroshima University School of Medicine, Japan.
Yokoyama
T
T
Tatsumoto
N
N
Hiyama
K
K
Imamura
Y
Y
Murakami
Y
Y
Kodama
T
T
Piatyszek
M A
MA
Shay
J W
JW
Matsuura
Y
Y
D001483:Base Sequence; D015139:Blotting, Southern; D004253:DNA Nucleotidylexotransferase / Q000737:chemistry / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000032:analysis; D005753:Gastric Mucosa / Q000201:enzymology; D006801:Humans; D008969:Molecular Sequence Data; D013274:Stomach Neoplasms / Q000201:enzymology*; D016615:Telomere
D004273:DNA, Neoplasm; D004253:DNA Nucleotidylexotransferase