Tags

Type your tag names separated by a space and hit enter

Alternative lengthening of telomeres frequently occurs in mismatch repair system-deficient gastric carcinoma.
Cancer Sci. 2009 Mar; 100(3):413-8.CS

Abstract

Maintenance of telomeric ends by the telomerase ribonucleoprotein complex or the telomerase-independent alternative lengthening of telomeres is necessary for the immortalization of human cells. The significance of alternative lengthening of telomeres has been suggested in DNA mismatch repair system-deficient cells; however, much remains unknown in human malignancies. In this study, we investigated the telomere maintenance mechanism in gastric carcinoma. In formalin-fixed and paraffin-embedded sections of the high frequency of microsatellite instability (MSI-H) and non-MSI-H gastric carcinomas, there was no difference in telomere length monitored by telomere intensity ratio using telomere-fluorescent in situ hybridization. Immunoreactivity of hTERT, the catalytic subunit of telomerase, was detected in 48% of MSI-H gastric carcinomas. The frequency was significantly lower than that in non-MSI-H gastric carcinomas (86%, P = 0.02). Conversely, the number of the alternative lengthening of telomeres-associated promyelocytic leukemia bodies (APBs) detected by combined promyelocytic leukemia immunofluorescence and telomere-fluorescent in situ hybridization was statistically higher (57%) in the MSI-H gastric carcinomas compared to that in non-MSI-H gastric carcinomas (19%, P = 0.026). The cases with hTERT(+)APBs(-) were more frequent in non-MSI-H gastric carcinomas (76%) than in MSI-H gastric carcinomas (24%), and the cases with hTERT(-)APBs(+) were more frequent in MSI-H gastric carcinomas (33%) than in non-MSI-H gastric carcinomas (10%). These results suggest that alternative lengthening of telomeres-mediated telomere maintenance plays an important role for microsatellite instability-mediated stomach carcinogenesis, as well as the telomerase ribonucleoprotein complex, although the incidence of MSI-H is low. Defects of the mismatch repair system may lead to homeologous recombination of telomeric ends for the telomerase-independent telomere maintenance in gastric carcinomas.

Authors+Show Affiliations

Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19154407

Citation

Omori, Yasuhiro, et al. "Alternative Lengthening of Telomeres Frequently Occurs in Mismatch Repair System-deficient Gastric Carcinoma." Cancer Science, vol. 100, no. 3, 2009, pp. 413-8.
Omori Y, Nakayama F, Li D, et al. Alternative lengthening of telomeres frequently occurs in mismatch repair system-deficient gastric carcinoma. Cancer Sci. 2009;100(3):413-8.
Omori, Y., Nakayama, F., Li, D., Kanemitsu, K., Semba, S., Ito, A., & Yokozaki, H. (2009). Alternative lengthening of telomeres frequently occurs in mismatch repair system-deficient gastric carcinoma. Cancer Science, 100(3), 413-8. https://doi.org/10.1111/j.1349-7006.2008.01063.x
Omori Y, et al. Alternative Lengthening of Telomeres Frequently Occurs in Mismatch Repair System-deficient Gastric Carcinoma. Cancer Sci. 2009;100(3):413-8. PubMed PMID: 19154407.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alternative lengthening of telomeres frequently occurs in mismatch repair system-deficient gastric carcinoma. AU - Omori,Yasuhiro, AU - Nakayama,Fumihito, AU - Li,Dong, AU - Kanemitsu,Kiyonori, AU - Semba,Shuho, AU - Ito,Akihiko, AU - Yokozaki,Hiroshi, Y1 - 2008/12/16/ PY - 2009/1/22/entrez PY - 2009/1/22/pubmed PY - 2009/3/26/medline SP - 413 EP - 8 JF - Cancer science JO - Cancer Sci. VL - 100 IS - 3 N2 - Maintenance of telomeric ends by the telomerase ribonucleoprotein complex or the telomerase-independent alternative lengthening of telomeres is necessary for the immortalization of human cells. The significance of alternative lengthening of telomeres has been suggested in DNA mismatch repair system-deficient cells; however, much remains unknown in human malignancies. In this study, we investigated the telomere maintenance mechanism in gastric carcinoma. In formalin-fixed and paraffin-embedded sections of the high frequency of microsatellite instability (MSI-H) and non-MSI-H gastric carcinomas, there was no difference in telomere length monitored by telomere intensity ratio using telomere-fluorescent in situ hybridization. Immunoreactivity of hTERT, the catalytic subunit of telomerase, was detected in 48% of MSI-H gastric carcinomas. The frequency was significantly lower than that in non-MSI-H gastric carcinomas (86%, P = 0.02). Conversely, the number of the alternative lengthening of telomeres-associated promyelocytic leukemia bodies (APBs) detected by combined promyelocytic leukemia immunofluorescence and telomere-fluorescent in situ hybridization was statistically higher (57%) in the MSI-H gastric carcinomas compared to that in non-MSI-H gastric carcinomas (19%, P = 0.026). The cases with hTERT(+)APBs(-) were more frequent in non-MSI-H gastric carcinomas (76%) than in MSI-H gastric carcinomas (24%), and the cases with hTERT(-)APBs(+) were more frequent in MSI-H gastric carcinomas (33%) than in non-MSI-H gastric carcinomas (10%). These results suggest that alternative lengthening of telomeres-mediated telomere maintenance plays an important role for microsatellite instability-mediated stomach carcinogenesis, as well as the telomerase ribonucleoprotein complex, although the incidence of MSI-H is low. Defects of the mismatch repair system may lead to homeologous recombination of telomeric ends for the telomerase-independent telomere maintenance in gastric carcinomas. SN - 1349-7006 UR - https://www.unboundmedicine.com/medline/citation/19154407/Alternative_lengthening_of_telomeres_frequently_occurs_in_mismatch_repair_system_deficient_gastric_carcinoma_ L2 - https://doi.org/10.1111/j.1349-7006.2008.01063.x DB - PRIME DP - Unbound Medicine ER -