Abstract 4287: <i>HABP2</i> p.G534E variant in patients with family history of thyroid and breast cancer
Bibliographic record
Abstract
Abstract Background. Familial Papillary Thyroid Carcinoma (PTC) has been recently associated with the HABP2 p.G534E mutation. In this study we evaluated the putative association of the HABP2 p.G534E mutation and familial history of PTC and Breast Carcinoma (BC) in the Brazilian population. Methods. Germline mutations of twenty unrelated individuals with personal and/or family history of PTC and/or BC were identified by whole exome sequencing (WES), using Nextera Exome Enrichment kit and HiSeq200 platform (Illumina). Two cases were positive for p.G534E. Family members from both positive cases (seven from Family 1 and three from Family 2) were recruited for segregation analysis. An additional patient and three relatives (Family 3) with history of PTC and BC were included for validation. Fifty frozen PTC tumor samples and 170 healthy Brazilian individuals were also screened for the HABP2 variant. Confirmation and validation were performed by Sanger sequencing. Results. Interestingly, Family 1 reported a consanguineous history, reflected in two homozygous cases: the proband (PTC) and his unaffected sister. Also, only one (BC) out of eight tested members was negative for p.G534E. In the Family 2, the only patient diagnosed with PTC was negative for the mutation, while three relatives were positive for the same loci. The index case (PTC) from Family 3, was wild type for HABP2 and three relatives tested were positive carriers. In PTC tumor samples the Allele Frequency (AF) was 0.04: two heterozygous and one homozygous for p.G534E. Among 170 healthy individuals, five were heterozygous for the variant, representing an AF of 0.0147. The two index patients evaluated by WES also presented interesting pathogenic variants in genes potentially associated with deregulation of the extracellular matrix organization pathway (CTSB, TNXB, COL4A3, COL16A1, COL24A1, COL5A2, NID1, LOXL2, MMP11, TRIM24 and MUSK) and DNA repair function (NBN and MSH2). Conclusion. Our findings suggest that HABP2 is not a predisposition gene involved in familial PTC and BC. Financial Support: FAPESP (2013/01867-8 and 2014/03983-8) and CNPq (481132/2012-0) Note: This abstract was not presented at the meeting. Citation Format: Maisa Pinheiro, Sandra A. Drigo, Fabio A. Marchi, Renata Tonhosolo, Sonia C. Andrade, Igor Jurisica, Luiz P. Kowalski, Maria Isabel W. Achatz, Silvia R. Rogatto. HABP2 p.G534E variant in patients with family history of thyroid and breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4287. doi:10.1158/1538-7445.AM2017-4287
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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 | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 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) | 0.004 | 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".