Abstract PD6-2: Identifying genomic signatures in circulating tumour cells from breast cancer
Notice bibliographique
Résumé
Abstract Introduction: Levels of circulating tumor cells (CTCs) in blood have prognostic value in early and metastatic breast cancer. CTCs also show varying degrees of concordance with the primary tumors they originate from. This is indicative of heterogeneity and dynamic evolution of tumor cells as they acquire new functionality. Profiling of CTCs will help identify occult changes occurring in breast cancer cells during progression to metastasis. CTCs could contain genomic alterations that define them as metastatic intermediates, and may be identified in primary tumors at low frequencies, as an aggressive component that responds differentially to chemotherapy. Methodology: CTCs and matched normal white blood cells were isolated from the blood of 17/40 chemonaive breast cancer patients. Copy number analysis was performed with the Affymetrix Genome-Wide Human SNP 6.0 array using a paired tumor-normal approach. Minimal common regions (MCRs) of gain were extrapolated, followed by unsupervised clustering. Associations between MCRs and breast cancer subtypes; as well as metastasis, were identified using PLINK analysis. A TCGA copy number dataset of 787 invasive primary breast tumors was queried for frequency of CTC-like alterations. Results: CTC genomic profiles clustered into 2 groups independent of subtype: a heterogeneous group with 11 MCRs (genes amplified: AKT2, SMAD2), and a more homogeneous group with 400 MCRs, of which 55 were on chromosome 19 (genes amplified: ANGPTL4, BSG). There were 2 MCRs in common, on 19q13 and 21q; containing genes involved in resistance to anoikis, TGFb signaling and metastasis (TFF3, LTBP4, NUMBL). A 1.2Mb region harboring the ERBB2 gene was gained in 15/17 samples. Patients with distant metastases and younger age (<50) clustered together. Region 19q13 was associated with HER2 positivity and triple negative status of matched primary tumors. Regions 20q13 and 15q34 were associated with distant metastases. CTC-like gains were identified at low frequencies of 3-4% in 787 primary tumors (genes amplified: CCNE1, KLK7-14, MIR371-373). Conclusions: The genomic profiles of CTCs clustered into 2 groups: a heterogeneous group with minimal alterations that may be sufficient for dissemination; and a more homogeneous group with extensive alteration, that could define those CTCs that may be en route to the next steps of metastasis. There were only 2 MCRs in common between the groups that highlights an important common point of evolution of CTC genomes. CTCs also appear to be more homogeneous for certain gains, specifically on chromosome 19, which may allow for CTC-like functionality such as invasion, intravasation, survival or chemo-resistance. Furthermore, CTC-like gains were identifiable at low frequencies within a dataset of primary breast tumors. We are currently using multispectral-FISH to examine the most frequent combinations of CTC-like gains in primary breast tumors pre- and post-chemotherapy. It is possible that CTC-like alterations, even if present only focally, could confer a more aggressive course of progression to metastasis. More importantly, these cells could be targeted to stop their spread to distant sites. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD6-2.
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 | 0,001 |
| 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 | 0,001 | 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) | 0,002 | 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 ».