Alternative lengthening of telomeres frequently occurs in mismatch repair system‐deficient gastric carcinoma
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Bibliographic record
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.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it