Telomere dysfunction in prostatic carcinogenesis: The crognostic importance of telomere length in HPIN (high-grade prostatic intraepithelial neoplasia)
Bibliographic record
Abstract
Proc Amer Assoc Cancer Res, Volume 47, 2006 4992 One of the major types of genetic instability in human malignancies is characterized by abnormal karyotypes, featuring both structural and numerical chromosome abnormalities and is termed chromosomal instability (CIN). CIN has been demonstrated in both carcinoma of the prostate (CaP) and high-grade prostatic intraepithelial neoplasia (HPIN). Both the chromosomal and genetic changes observed in HPIN are similar to those seen in primary CaP. Telomeres are the terminal repeated DNA sequence associated with specific binding proteins of eukaryotic chromosomes. Natural shortening of telomeres with each cell division has been thought to act as a mitotic clock limiting the replicative potential of the cell. Excessive telomere shortening leads to end-to-end chromosomal fusion thereby to unstable chromosomal rearrangements and cell death. This laboratory previously found a significant decrease in telomere length in both HPIN and CaP in comparison to normal prostatic epithelium and more erosion evident in HPIN in the discrete regions of the prostate containing CaP. Therefore we hypothesise that the loss of telomere integrity and the resulting chromosomal instability (CIN) is an early fundamental event in CaP oncogenesis and that measurement of telomere length in HPIN associated with telomere dysfunction will provide prognostic information about progression to CaP and clinical outcome. We have analysed sextant core biopsies from 80 patients with HPIN from 1998-2000 (41 diagnosed subsequently with CaP and 39 without CaP on rebiopsy) with a minimum clinical and pathological follow up of 4 years. To correlate the morphology of fluorescently labelled and DAPI-counterstained tissue sections containing HPIN, an adjacent H&E section has been obtained for each biopsy studied. To examine telomere length distribution within HPIN in the cohort, we have used quantitative fluorescence in-situ hybridisation (Q-FISH) analysis of interphase nuclei in paraffin embedded sections with directly labelled telomere specific PNA probes as the resulting fluorescence emission is known to be directly proportional to telomere length. Internal control probes for centromere intensity have also been used. Current pathways of HPIN to CaP involving genes such as PTEN and ETS transcription factors are simultaneously being investigated. Statistical associations between telomere length in the HPIN sample, gene detection and the subsequent diagnosis of cancer and the Gleason score will be reported. These analyses will help determine whether telomere erosion provides a useful biomarker for the development of prostate cancer and reveal mechanisms underlying genomic instability in this neoplasm.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".