Pathogenesis of hereditary tumors: beyond the “two‐hit” hypothesis
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Knudson's 'two-hit' hypothesis has provided extremely important insights into the pathogenesis of tumors in autosomal dominant tumor predisposition syndromes, but recent evidence suggests that some such tumors may occur without a 'second hit' or require more than two mutations. Inactivation of both RB1 alleles appears to be insufficient by itself to cause malignancy in the tumors that develop in patients with hereditary retinoblastoma. On the other hand, certain tumors in patients with tuberous sclerosis complex appear to develop in haploinsufficient tissues that do not have 'second hit' mutations of a tuberous sclerosis gene. The molecular pathogenesis of certain other tumors in patients with tuberous sclerosis complex or neurofibromatosis 1 may not be fully explained by the 'two-hit' hypothesis either. Hereditary tumors, like non-hereditary tumors, may arise by a variety of molecular mechanisms, with loss of both alleles of a particular tumor suppressor gene being a frequent, but not invariably necessary or sufficient, event. Four models are presented to explain how various tumors may arise in patients with inherited tumor predisposition syndromes such as hereditary retinoblastoma, tuberous sclerosis complex or neurofibromatosis 1. Even tumors of one particular type may develop by more than one mechanism.
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.
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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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