Abstract 4747: Genomic alterations in ductal carcinoma in situ compared with Invasive breast cancer: a quantitative real-time PCR study
Notice bibliographique
Résumé
Abstract Introduction: Several molecular markers have been investigated as possible prognostic factors for ductal carcinoma in situ (DCIS) progression to invasive ductal cancer (IDC). DCIS is regarded as a non-obligate precursor of IDC as it is frequently found adjacent to or surrounded by invasive breast cancer. Previously, we carried out genomic analyses that demonstrated that DCIS has specific genetic alterations that were conserved in invasive disease. Nevertheless, it is still unknown whether DCIS is merely a marker of increased risk, or actually a driver of the progression to IDC.Thus, it is crucial to better understand the genetic aberrations that underlie DCIS progression to IDC. Methodology: We conducted array chromosomal genomic hybridization on pure DCIS, IDC and DCIS paired with IDC, with 30 cases each (all were microdissected). Three chromosomal regions were selected based on the rate of their detection, which was significantly different (p<0.05) between tumors of different receptor status, whether in combination, or single parameter; ER, PgR, HER2. In total, 9 genes were chosen for further validation, spanning Chromosome 4p15.33, Chromosome 5q11.2 and Chromosome 5q31.3. Quantitative real-time polymerase chain reaction (Q-RT-PCR) was used to study the copy number state of the 9 genes in different pure cases, including 22 DCIS, 29 IDC and 10 DCIS paired with IDC (all were microdissected). All areas contained more than 90% carcinoma or control cells. By normalizing values to the housekeeping gene, human albumin, and normal control DNA samples, we obtained ΔΔCt values for each sample. Results: 61 samples were analyzed by comparing DCIS and IDC copy numbers of genes within the selected chromosomal regions. The median relative gene quantities were 1.66(4p15.33), 1.34(5q11.2) and 1.25(5q31.3). In all regions, IDC showed higher levels of amplification than DCIS with varying degrees of significance. Not all differences between DCIS and IDC in individual genes were significant. This observation may be attributed to focal variations in gene copy numbers and noise from Q-RT-PCR methods. 4p15.33 and 5q31.3 regions demonstrated significant gain in IDC compared to DCIS (p = 0.021). Genes within these regions include miRNA 572 (MIR572) and integrin alpha 2 (ITGA2). MIR572 is known to be involved in post-transcriptional regulation of gene expression, whereas ITGA2 encodes the alpha subunit of a transmembrane receptor for collagens. In the Chromosome 5q31.3 region, paired samples of DCIS and IDC also showed a trend in gene copy numbers, with IDC having a higher value than DCIS. Conclusions: Our findings demonstrate that there are specific genetic alterations associated with DCIS progression to IDC. In particular, MIR572 within Chromosome 4p15.33 and ITGA2 within Chromosome 5q31.3 may serve as candidate regions to predict the progression of DCIS to IDC. Note: This abstract was not presented at the meeting. Citation Format: Trillium E. Chang, Keisha Warren, Ranju Nair, Tian Y. Lu, Adewunmi Adeoye, Vladimir Iakovlev, Susan J. Done. Genomic alterations in ductal carcinoma in situ compared with Invasive breast cancer: a quantitative real-time PCR study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4747. doi:10.1158/1538-7445.AM2015-4747
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 | 0,001 | 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 | 0,000 | 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) | 0,003 | 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 ».