Prevalence of <i>PALB2</i> mutations in the Creighton University breast cancer family registry.
Bibliographic record
Abstract
e12519 Background: PALB2 (i.e., the partner and localizer of BRCA2) plays an important role in double-strand DNA damage repair through interaction with BRCA1, BRCA2, and RAD51. Xia et al. (Nat Genet 2007;39:159-161) determined that homozygous mutations in PALB2 cause Fanconi’s anemia. Studies by Chen et al. (Clin Cancer Res 2008;14:5931-5937) and Janatova et al. (Cancer Epidemiol Biomarkers Prev 2013;22:2323-2332) found that, based on women with a family history of breast cancer, those who carried heterozygous mutations in PALB2 had an increased risk of developing hereditary breast cancer. Furthermore, a recent large-scale PALB2 predisposition study by Antoniou et al. (N Engl J Med 2014;371:497-506), indicates that the risk of breast cancer among PALB2 heterozygous mutation carriers is comparable to those of pathogenic BRCA2 mutation carriers, with a higher risk among those younger than 40 years of age; the breast cancer risk by age 70 is as high as 35%. According to Nguyen-Dumont et al. (Breast Cancer Res Treat 2015;149:547-554), germline heterozygous loss-of-function mutations in PALB2 are responsible for approximately 2.4% of familial breast cancer. Methods: The PALB2 gene was screened for mutations in 90 unrelated breast cancer families from Creighton’s Breast Cancer Family Registry who had previously tested negative for mutations in BRCA1 and BRCA2. All 13 coding exons of PALB2 plus 20 bp from both sides of each exon were amplified using Wafergene SmartChip Technology and sequenced by Illumina MiSeq next generation sequencer. Results: Two of 90 breast cancer probands (2.2%) were found to carry a truncating mutation in PALB2 (c.2411_2412delCT and c.2053delC). Both probands were diagnosed with breast cancer before the age of 35 and had three relatives with breast cancer. This early age of onset is consistent with findings by Nguyen-Dumont et al. (Breast Cancer Res Treat 2015;149:547-554). Also several missense variants with unknown clinical significance were identified among screened patients. Conclusions: Mutations of PALB2 are rare but testing for PALB2 mutations is a useful adjunct for patients undergoing testing for BRCA1 and BRCA2.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.004 | 0.005 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.011 | 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 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".