Effects of genomic imbalances on telomerase activity in gastric cancer: clues to telomerase regulation.
Telomerase is a specialized cellular reverse transcriptase that adds telomeric repeats (TTAGGG) at the ends of each chromosome. Nearly the complete spectrum of human cancers has been shown to be telomerase positive. The understanding of the telomerase regulation in concert with other genetic alterations in the process of malignant transformation of human cells has important clinical and practical implications. Regulation of telomerase activity (TA) is highly complex, and both putative positive and negative regulators have been reported. However, the mechanisms involved in telomerase regulation are not fully established. Identification of additional telomerase components and associated proteins will certainly contribute to further investigations of the effect of telomerase in telomere elongation, telomere length maintenance, oncogenesis, and functionally new, unidentified cellular functions. In this study our aim was to determine the chromosomal localizations of putative unidentified telomerase activator(s) and/or repressor(s) by high resolution-comparative genomic hybridization (HR-CGH) in highly telomerase expressing gastric tumor samples. For this purpose TAs and genomic imbalances were identified in the same tumor samples and relation between these was evaluated. Genomic changes affecting telomerase activity in 50 gastric tumor samples were investigated by HR-CGH. We have found that genomic imbalances including 1q+, 8p+, 8q+, 10q+, 17p-, and 20p+ are associated with the higher telomerase activity. Our results suggest that 1q24, 8p21-p11.2, 8q21.1-q23, 10q21-qter and 20pter-p11.2 may contain putative telomerase activator(s), whereas the 17p12 region may harbor candidate telomerase suppressor(s).
Gümüş-Akay
Güvem
G
Department of Medical Biology, Ankara University Faculty of Medicine, Ankara, 06100, Turkey.
Elhan
Atilla Halil
AH
Unal
Ali Ekrem
AE
Demirkazik
Ahmet
A
Sunguroğlu
Asuman
A
Tükün
Ajlan
A
D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D042822:Genomic Instability; D006801:Humans; D013274:Stomach Neoplasms / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*
D019098:Telomerase