Abnormalities Of FAM46C, AHCYL1, CDC14A and CDKN2C Genes Located At Chromosome 1p Detected By QM-FISH Identifies Deletion Of 1p32.3 Covered CDKN2C Is An Independent Adverse Prognostic Marker In Multiple Myeloma
Notice bibliographique
Résumé
Abstract SNP arrays and FISH showed Chromosome 1 appeared as a critical region in MM pathogenesis and was associated with adverse survival, such as: 1q gain and 1p deletion. Recent years, some studies found deletions of some genes in the common minimum deletion regions on 1p were related to adverse prognosis, such as FAM46C at 1p12, CDC14A at 1p21.2, CDKN2C at 1p32.3. However, these studies were limited to one or two regions and lacked the comparison among the effects of different sites on prognosis. The characteristics of chromosome 1p abnormalities are not clear and no uniform consensus has been obtained that which locus is the best prognostic factor suitable for clinical routine detection. In addition, there's lack of data on the impact of 1p abnormalities on homogeneous group of patients. We investigated the abnormalities of FAM46C, AHCYL1, CDC14A, CDKN2C genes located at chromosome 1p12, 1p13.3, 1p21.2 and 1p32.3 by quantitative multicolor-fluorescence in situ hybridization (QM-FISH) using bacterial artificial chromosome (BAC) clones in 230 previously untreated myeloma patients. FAM46C, AHCYL1, CDC14A, CDKN2C genes were labeled with Green-dUTP (green), promoFluor-555-aadUTP (orange), PF590-dUTP (Red) and PF415-dUTP (Blue) and used as a FISH probe. The results demonstrated the deletion rates of 1p12, 1p13.3, 1p21.2 and 1p32.3 were 13.0%, 18.7%, 20.8% and 9.06% respectively. The deletion rate of 1p was 24.2%. Amplifications of 1p with 3.04%, 2.60%, 3.77% and 4.15% respectively in 1p12, 1p13.3, 1p21.2 and 1p32.3 were detected in some patients. These amplifications were significant lower than those of deletions (P=0.000, 0.000, 0.000, 0.021). Interestingly, we found chromosome 1p abnormalities were complex, various in forms. Among 57 patients with del(1p), 26.3% of patients presented with one locus deletion, 22.8% with two loci loss, 35.1% with three loci loss, 15.8% with four loci loss. Most (73.7%) of del (1p) were large size of deletion (≥ two regions). Del (1p) was positively correlated with high LDH (≥220U/L) (P=0.026), del (13q14) (P=0.023), and high percentage of plasma cells in bone Marrow (≥ 50%) (P=0.001). 108 patients were homogeneously treated with thalidomide-based chemotherapy (TAD/MPT). Survival analysis showed the median progression-free survival (PFS) of patients with and without del (1p) were 13.0 vs.26 months (P=0.002), median overall survival (OS) were 15.5 vs. 39.5 months (P=0.000). In addition, we found patients with sole del (1p) involving 1p12 or/and 1p13 had no worse prognosis. Patients with del (1p32.3) had shorter PFS (9.0 vs. 23.0, P=0.001) and OS (9.0 vs. 39.0, P=0.000). In multivariate analyses, 1p32.3 deletion appeared as an independent negative prognostic factor regarding to complex karyotype, LDH≥220U/L and del (17p13) in thalidomide-based chemotherapy group. Hazard ratio showed that the progression risk and death risk in patients with 1p32.3 were increased 5.64 (P=0.031) and 8.314 times respectively (P=0.011). Conclusion our datas show that chromosome 1p abnormalities are complex, various in forms, mainly with large size of deletion, rarely amplification. 1p deletions are negative prognostic factors for PFS and OS in MM patients receiving thalidomide-based chemotherapy. 1p32.3 deletion is the most important 1p deletion and is an independent poor factor. Disclosures: No relevant conflicts of interest to declare.
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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) | 0,002 | 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 ».