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Record W2029939216 · doi:10.1158/0008-5472.can-07-5835

Cancers Exhibit a Mutator Phenotype: Clinical Implications

2008· review· en· W2029939216 on OpenAlexfundno aff
Lawrence A. Loeb, Jason H. Bielas, Robert A. Beckman

Bibliographic record

VenueCancer Research · 2008
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsnot available
FundersNational Cancer InstituteTerry Fox Foundation
KeywordsPhenotypeBiologyMutationCarcinogenesisCancerGeneticsMutation rateCancer researchGene

Abstract

fetched live from OpenAlex

Malignancies are characterized by mutations. We have hypothesized that the thousands of mutations in most human cancers do not result from the low mutation rates exhibited by normal human cells. Instead, cancer cells express a mutator phenotype (i.e., the mutation rate in the cancer cells is much greater than that in normal cells). We consider the following points: (a) Mutations in genes that govern genetic stability could be the cause of a mutator phenotype exhibited by human cancers. (b) A mutator phenotype increases the efficiency of acquiring mutations including those associated with cancer. (c) Recent experimental evidence indicates that human tumors contain a vast array of both clonal mutations and nonexpanded (random) mutations. (d) The presence of nonexpanded mutations in tumors has fundamental clinical implications for cancer risk assessment, grading, and prognosis including the rapid emergence of resistance to chemotherapeutic agents. Lastly, (e) if a mutator phenotype drives carcinogenesis, drugs that target mutator pathways might prevent cancer by delay.

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 imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.004
Threshold uncertainty score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.002
Science and technology studies0.0000.001
Scholarly communication0.0010.002
Open science0.0010.001
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0040.003

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.

Opus teacher head0.215
GPT teacher head0.524
Teacher spread0.309 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview

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".

Quick stats

Citations222
Published2008
Admission routes1
Has abstractyes

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