Abstract 3410: Identification of frequently gained genomic regions in breast circulating tumor cells
Notice bibliographique
Résumé
Abstract Introduction: Cells disseminate from the primary tumor and enter the blood circulation early on. Circulating tumor cells (CTCs) might be the earliest detectable cells with metastatic abilities. Clinically, the presence of CTCs is indicative of a negative prognostic impact. Decreased numbers of CTCs are seen in response to chemotherapy, and persistent chemo-resistant CTCs have been shown to be HER2+ although they originated from HER2- primary tumors. Such discrepancies were also found with ER, PR and EGFR status and have important implications with respect to treatment alterations over the course of the disease. If the whole genome of CTCs can be profiled, we could identify genomic alterations which may be developed into CTC specific markers, to monitor and target them, to prevent their spread to distant sites. We could also investigate how these cells are represented in primary tumors and how they respond to chemotherapy. Methods: CTCs were enriched from blood by immunomagnetic CD45+ leukocyte depletion; fixed onto glass slides and stained for the epithelial cell marker, pancytokeratin. Positively stained CTCs were isolated by single-cell laser capture microdissection for whole genome amplification (WGA) and copy number (CN) analysis with the Affymetrix Genome wide SNP 6.0 array. CTCs were isolated from peripheral blood of 21/39 patients (54%, range of 1-20 cells) with locally advanced breast cancer. Normal samples were obtained by performing WGA on the white blood cell fraction of blood. Results: CN gains and losses were detected by genomic segmentation, using a paired CTC-normal sample approach (Partek Genomic Suite). Overall, regions with gains were more prevalent than losses. The most frequent gains were on chromosome 1q21.3, 4q26, 6q16.3, 9q34.1-34.3, 11p15.4-15.5, 17q21-25, and 19. Regions 17q21-25 and 9q34 were associated with lymph node metastasis, tumor size, and higher CTC counts. Genes within these regions which could potentially be implicated in CTC dissemination are CCL5 (breast cancer progression), MMP28 (invasion), and PTPN1 (migration). Notably, CTCs were more homogenous for gains on chromosome 19, which has been implicated in many types of cancers. It houses the entire family of kallikrein protease genes, a hallmark in prostate, ovarian and colorectal cancers; and was recently found to contain 5 SNPs which are associated with BRCA1 mutations and high risk breast cancer. We identified 5 peaks (0.3 - 9.5Mb) between 19p13.3-13.1 and 19q13.32-13.4, with an average CN of 3, in 15/17 patients. Conclusions: Whole genomic profiling of CTCs from breast cancer revealed regions of CN gain, as well as specific CN signatures associated with poor prognosis. Gains on chromosome 19 were most frequent, warranting further investigations of genes that confer CTC-like functionality to tumor cells. We will determine the heterogeneity of these regions in primary breast cancer, and how they respond to chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3410. doi:1538-7445.AM2012-3410
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 | 0,001 | 0,001 |
| 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) | 0,004 | 0,001 |
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 ».