Abstract 3535: Whole genome sequencing of single circulating tumor cells from localized high-risk prostate cancer patients: Laser microdissection and 3Dtelomere profile
Notice bibliographique
Résumé
Abstract Advances in the development of precision medicine for prostate cancer patients rely on accurate identification of the genomic features underlying a patient's tumor. Genomic analysis of circulating tumor cells (CTCs) could provide a unique and accessible representation of tumor diversity, however for the use of CTCs as a less-invasive sampling of prostate cancer and as biomarkers for patient stratification and selection of targeted therapy, complex platforms are necessary to ensure an efficient enrichment (isolation), detection (identification-imaging) and characterization strategies (molecular profiles). In this study, we combined a filtration-based CTC isolation technology with prostate cancer cell-specific antibodies to identify the prostate cancer CTCs. After identification, we performed the 3D telomere profiling prior to laser microdissection for whole genome sequencing of singles CTCs from 11 localized high-risk prostate cancer patient samples (36 CTCs in total). We identified unique and common somatic single nucleotide variants (SSNVs) and copy number alterations (CNAs) that can be used to predict high-risk lethal prostate cancer and treatment response in patients with clinically localized high- risk prostate cancers. The distribution of telomeres intensities show a range between 0 to 190.000 (a.u) and telomeres parameters were similar as described previously for high risk patients by our group. We analyzed 36 CTCs from 11 different patient samples and compared with normal lymphocytes from the same patient using whole genome sequencing (WGS). We identified 184 common mutated genes in all CTCs and two mutated genes with the same base pair (bp) mutation (PMS2 and EIF2AK4). We also identified 503 consensus mutations found in all patient but not in all CTCs and 1728 unique mutations found in all or any CTCs of only one patient, showing the heterogeneity that arises in single cells. The list of genes affected are all involved in potential pathways for tumor development such as immune system, signal transduction, homeostasis, gene expression, chromatin organization, DNA repair, cell cycle, programmed cell death, cell-cell communication and others. MCPH1, also known as BRIT1, is a key regulatory gene of the DNA damage response pathway and was mutated in all CTCs from prostate patients. MCPH1 deficiency promotes genomic instability and increases cancer susceptibility. The PMS2 gene is a member of a set of genes known as the mismatch repair (MMR) genes which promotes also genomic Instability. Those mutations can be closely linked with the genomic instability we found assessing the telomere profiles. The CDH17 gene is a member of the cadherin superfamily and in contrast to classic cadherins, such as E- and N-cadherin, LI-cadherin possess biological functions distinct from classic cadherins and reduced expression of LI-cadherin is closely associated with tumor progression and lymph node metastasis of human colorectal carcinoma. These mutations were also found in all CTCs. All this information is needed for individualized therapy and predict drug resistance, phenotypic transition which is heterogeneous from cell to cell from patient to patient. Citation Format: Aline Rangel Pozzo. Whole genome sequencing of single circulating tumor cells from localized high-risk prostate cancer patients: Laser microdissection and 3Dtelomere profile [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3535.
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 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 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) | 0,001 | 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 ».