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Abstract PO-093: Circulating tumor DNA (ctDNA) from peripheral blood is detectable among Ghanaian breast cancer patients

2020· article· en· W3109613928 on OpenAlexaff
Samuel Terkper Ahuno, Lawrence Edusei, Nicolas Titiloye, Ernest Adjei, Joe‐Nat Clegg‐Lamptey, Joel Yarney, Beatrice Wiafe‐Addai, Baffour Awuah, Verne Vanderpuye, Máire A. Duggan, Seth Wiafe, Kofi Nyarko, Francis Aitpillah, Daniel Ansong, Thomas U. Ahearn, Alexander Kwarteng, Mustapha Abubakar, Montserrat García‐Closas, Gavin Ha, Jonine D. Figueroa, Paz Polak

Bibliographic record

VenueCancer Epidemiology Biomarkers & Prevention · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsUniversity of Calgary
Fundersnot available
KeywordsBreast cancerConcordanceMedicineInternal medicineOncologyCancerCopy-number variationBiologyGeneGenomeGenetics

Abstract

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Abstract Cancer incidence is rising and mortality rates are high in Africa, where access to molecular pathology is limited. Analysis of cancer-related mutations in circulating tumor DNA (ctDNA) from cell-free DNA (cfDNA) that is shed into the bloodstream by tumor cells could be transformative to the African continent and provide new molecular insights. Using samples collected from the Ghana Breast Health Study we tested whether whole-genome sequencing (WGS) of cfDNA could detect ctDNA and identify somatic alterations that drive breast cancer. We selected 15 breast cancer patients (median age 49.5 years) with duplicated plasma samples. Pathologic grade, age, and immunohistochemical (IHC) stains for estrogen receptor (ER), progesterone receptor (PR) and HER2 were available for the majority of patients (>80%). cfDNA extraction and WGS at 30x and 0.1x was performed. ichorCNA software was used on Next Generation Sequencing (NGS) read counts to estimate the ctDNA fraction and predict copy number alteration profiles. High depth 30x cfDNA-WGS analysis showed that all 15 breast cancer patients had 1% ctDNA or greater (median[IQR] 3.96%[2.22%-8.13%]). There was high concordance between estimated ctDNA fraction using 0.1x and 30x WGS (Pearson r = 0.9). Copy number profiling showed extensive amplification and deletion of multiple chromosomal regions containing important cancer genes (such as MYC, PIK3CA, TERT, and GATA3). Of the four patients classified as HER2 positive based on IHC, two had increased ERBB2 copy number (50 and 3 copies, respectively). Our data provide evidence that ctDNA-based genomic studies are possible and ctDNA analysis could be a tool for future molecular oncology studies in Africa for cancer etiology, surveillance and clinical trials. Citation Format: Samuel T. Ahuno, Lawrence Edusei, Nicolas Titiloye, Ernest Adjei, Joe-Nat Clegg-Lamptey, Joel Yarney, Beatrice Wiafe-Addai, Baffour Awuah, Verne Vanderpuye, Maire Duggan, Seth Wiafe, Kofi Nyarko, Francis Aitpillah, Daniel Ansong, Thomas Ahearn, Alexander Kwarteng, Mustapha Abubakar, Montserrat Garcia-Closas, Gavin Ha, Jonine D. Figueroa, Paz Polak, on behalf of the Ghana Breast Health Study Team. Circulating tumor DNA (ctDNA) from peripheral blood is detectable among Ghanaian breast cancer patients [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-093.

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)0.000
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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

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.

Opus teacher head0.021
GPT teacher head0.281
Teacher spread0.260 · 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 designObservational
Domainnot available
GenreEmpirical

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".

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Citations0
Published2020
Admission routes1
Has abstractyes

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