Genetic Variations in Multiple Myeloma with Extramedullary Disease
Notice bibliographique
Résumé
Background Extramedullary disease (EM) is aggressive form of MM in which clonal plasma cells exist outside the BM. EM may be found in up to 30% of MM patients and is associated with an adverse prognosis. However, the genetic pathogenesis of EM have not yet been precisely elucidated. Patients and Methods From 2005 to 2020, among patients diagnosed with MM with EM (EMM) confirmed by image study, a total of 12 patients for whom tumor tissue or BM specimens could be obtained were enrolled. Both bone-related EM (EM-B) and soft-tissue-related EM (EM-S) were defined as EM. We performed whole-exome sequencing (WES) and NanoString nCounter assay to investigate the genetic alterations in EMM patients. A total of 9 formalin-fixed paraffin-embeded (FFPE) tumor tissues and 6 BM specimen from 12 EMM patients were sequenced. Paired BM and FFPE were available for analysis in 3 patients. To clarify the genetic difference between MM and EMM, 8 BM samples of 5 MM patients were analyzed as controls. In addition, 4 buccal swabs from one EMM patient were sequenced for germline control. Results The median age was 57 years (range 50-65). Two patients had EM-S involving meninges and Lt. psoas muscle showed adverse prognosis compared to patients with EM-B, with survivals of 1 month and 11 months after diagnosis of EM. One of them had a gain (1q21) chromosomal aberration classified as high risk cytogenetics. WES was performed on 12 EMM cases (BM=6, FFPE=8). In WES, MAP2K3, AHNAK2, CDC27, MUC4, and NBPF1 were the five genes with the most variation in both BM and FFPE (Fig. 1). In particular, CDC27 gene was altered only in FFPE (6 out of 8 samples). We performed RNA analysis by NanoString in 9 EMM patients (BM=6, FFPE=6) and 5 MM patients. Compared with MM, ARG1, IRF4, and CEP55 were up-regulated and CDKN1C, IL15, and CD3E were down-regulated in the BM of EMM. Comparison of BM specimens from MM and plasmacytoma from EMM showed IRF4 up-regulation in EMM. In plasmacytoma, chemokine and chemokine receptor related genes such as CXCL8, S100A9, S100A8, CCR4, CXCR2, and CXCR4 were down-regulated. Up-regulation of IRF4 was also observed in EMM when comparing normal buccal swab and EMM specimens. Conclusions In our study, significant genetic alterations have been identified. Especially, in WES analysis, CDC27 was mutated only in FFPE of EMM patients, and in Nanostring analysis, IRF4 was up-regulated all EMM samples. Further studies are needed to confirm the genetic alterations in more EMM patients.
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 | 0,000 | 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 | 0,000 |
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 ».