Abstract 4905: Mosaic chromosomal alterations overlapping hotspot and coldspot sites of somatic structural variation are associated with increased odds of hematological malignancy
Notice bibliographique
Résumé
Abstract BACKGROUND: Clonal hematopoiesis (CH) occurs when hematopoietic cells acquire somatic mutations and proliferate to generate clones in blood. CH can be driven by mosaic chromosomal alterations (mCAs), which are large somatic structural variants, and is associated with increased risk of blood malignancy. We conducted a genome-wide search for sites significantly more or less impacted by mCA events, termed hotspots and coldspots. We tested whether the odds of blood malignancy in participants harboring mCAs overlapping hotspots or coldspots differed from the overall association between mCAs and blood malignancy. METHODS: This study utilized two cohorts of the Canadian Partnership for Tomorrow’s Health, including the Ontario Health Study (OHS; n=7070) and CARTaGENE (n=28,639). Participants were genotyped with the UK Biobank Axiom or Infinium Global Screening Array and completed a baseline cancer questionnaire. All mCA calling was performed using MoChA software. We identified hotspot and coldspot sites of autosomal mCA accumulation using binomial tests scaled by chromosome and array type. We determined whether the number of overlapping mCAs at each query site was greater or less than would be expected under the null expectation. Then, we calculated the prevalence of cancer in participants with or without mCAs overlapping hotspots/coldspots and conducted Fisher’s exact tests to generate odds ratios. RESULTS: In OHS, participants with an mCA had a significantly greater odds of having a hematological malignancy at baseline (OR=7.29, 95% CI=3.72-13.38, p=7.84e-08). They were also more likely to have a cancer diagnosis of any type (OR=1.63, 95% CI=1.14-2.30, p=5.59e-03). Participants with an mCA overlapping a hotspot site had a further increased odds of harboring hematological malignancy (OR=9.79, 95% CI=3.94-21.29, p=5.05-e06). For participants with an mCA overlapping a coldspot site, the OR reached 20.52 (95% CI=3.68-76.85, p=7.36e-04). In CARTaGENE, participants with an mCA were also at increased odds of hematological malignancy (OR=11.31, 95% CI=6.78-18.17, p=9.77e-16), and any cancer diagnosis (OR=1.93, 95% CI=1.53-2.41, p=5.95e-08). Those carrying an mCA overlapping a hotspot site were 14.6 times more likely to have a hematological malignancy (95% CI=7.94-25.29, p=3.30e-13), and those with an mCA overlapping a coldspot site were 14.2 times more likely (95% CI=5.0-32.9, p=7.63e-06). CONCLUSIONS: These results suggest that there may be genomic locations at which somatic structural variation has a larger impact on the development of blood malignancy, relative to other regions. Further work is needed to characterize the functional consequences of somatic mutation at these key regions and explore whether these associations of hotspots, coldspots, and cancer incidence are conserved across a range of tissues. Citation Format: Jasmine Ryu Won Kang, Vanessa Bruat, Kimberly Skead, Mawusse Agbessi, June Kim, Elias Gbeha, Marie-Julie Fave, Philip Awadalla. Mosaic chromosomal alterations overlapping hotspot and coldspot sites of somatic structural variation are associated with increased odds of hematological malignancy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4905.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,008 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».