FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2564026582> ?p ?o ?g. }

• W2564026582 abstract "Abstract Background: Despite modern chemoimmunotherapy more than a third of patients with diffuse large B cell lymphoma (DLBCL) will experience relapse or refractory disease. Multiple mutations associated with the biology of DLBCL have recently been identified by next-generation sequencing in primary tumor samples, but little is known about their prognostic role. Furthermore, histological comparison of the primary tumor and relapsed disease is often not available in clinical practice due to the lack of centralized assessment and complicated by the difficulties to perform exome-wide sequencing in formalin fixed tissues. Therefore, the role of certain mutations and their mechanisms in clonal evolution during relapse is unknown and the rising of chemo-resistant DLBCL subclones has not been described in the literature so far. Methods: We identified all patients with available histologically confirmed relapsed or refractory DLBCL in our single center cohort of 346 patients with aggressive lymphoma treated at our tertiary cancer center in Salzburg, Austria. Primary formalin fixed paraffin embedded tumor sample, sample of refractory or relapsed disease and matched germ line were available for targeted next generation sequencing in 27 patients. A targeted exon capture and next-generation sequencing of all coding exons of 104 selected genes known to be frequently mutated in lymphoma were performed on a HiSeq 2500. Results: Sequencing was successful in 96.8% of all samples resulting in 25 patients with sequencing of the primary tumor and 24 patients with available pairs of primary lymphoma and histologically confirmed relapse. In these 24 patients two relapse samples were available in 10 patients and three relapse samples in one patient. Non-synonymous mutations were present in 74 of the 104 genes tested. Individual tumor samples showed between 0 and 29 non-synonymous mutations (median: 10). Less than six non-synonymous mutations in the primary tumor were associated with a better median OS than more mutations (28 versus 15 months p=0.031). We also compared the frequency of mutated genes in our cohort consisting of high risk patients defined by actual relapse with the literature containing patients with extensive sequencing but only little clinical data and clinical follow-up. Common mutated genes such as CARD11, CD58, CD79B, CREBBP, EZH2, BTG1 or B2M showed no difference in frequency to our patient cohort indicating no or only small driver function in resistant or refractory disease. Nevertheless, mutations previously reported to be at low frequency in DLBCL were significantly more often observed in our primary samples (NOTCH1, MYC, RB1, FAT2, ATM, SMARCA4, BCL7A) and relapsed samples (TP53, MCL1, ATM, FAT2, MYC, RB1, SMARCA4) of high risk patients when compared to the literature. We also observed the gain and the loss of several mutations between first diagnosis and histologically confirmed relapse. Overall, we observed an increase of the amount of non-synonymous mutations at first relapse in 12, no change in 6 and a decrease in 6 paired cases. A completely stable pattern of non-synonymous mutations was detected in 4 cases, but in the majority of cases relevant dynamic was observed: e.g.: gain of non-synonymous mutations in the p53 gene was seen in 3 patients (5 mutations), in the TNFRSF-14 gene in 2 patients (3 mutations), in the RB1 gene in 1 patient (1 mutation), in the NOTCH2 gene in 3 patients (4 mutations) and in the MYD88 gene in 1 patient (1 mutation) or loss of non-synonymous mutations in the CREBBP gene in 3 patients (3 mutations) or in the CRAD11 gene in 2 patients (2 mutations). Monitoring of subclones during disease was also possible using the allelic fraction over time e.g.: showing an increase of the NOTCH1 mutation burden in 2 biopsies after first diagnosis. Discussion: To the best of our knowledge clonal evolution detected by next generation sequencing has not been reported in DLBCL so far. We demonstrate the feasibility of such an approach from fixed tissue samples and using a curated set of target genes. In analogy to other lymphoid malignancies we can show the increase of allelic burden of certain mutations over time and the loss or gain of several others. While this approach is limited by the bias introduced by the selection of genes in the gene set, we feel that deep sequencing of selected mutations will provide further insights into subclone dynamics, which may be responsible for clonal evolution. Disclosures No relevant conflicts of interest to declare." @default.
• W2564026582 created "2017-01-06" @default.
• W2564026582 creator A5002179064 @default.
• W2564026582 creator A5006219111 @default.
• W2564026582 creator A5010743128 @default.
• W2564026582 creator A5026688095 @default.
• W2564026582 creator A5039762705 @default.
• W2564026582 creator A5039994927 @default.
• W2564026582 creator A5041163911 @default.
• W2564026582 creator A5048714300 @default.
• W2564026582 creator A5052246323 @default.
• W2564026582 creator A5077253651 @default.
• W2564026582 creator A5080576155 @default.
• W2564026582 date "2014-12-06" @default.
• W2564026582 modified "2023-09-27" @default.
• W2564026582 title "Clonal Evolution in Relapsed or Refractory Diffuse Large B Cell Lymphoma" @default.
• W2564026582 doi "https://doi.org/10.1182/blood.v124.21.77.77" @default.
• W2564026582 hasPublicationYear "2014" @default.
• W2564026582 type Work @default.
• W2564026582 sameAs 2564026582 @default.
• W2564026582 citedByCount "0" @default.
• W2564026582 crossrefType "journal-article" @default.
• W2564026582 hasAuthorship W2564026582A5002179064 @default.
• W2564026582 hasAuthorship W2564026582A5006219111 @default.
• W2564026582 hasAuthorship W2564026582A5010743128 @default.
• W2564026582 hasAuthorship W2564026582A5026688095 @default.
• W2564026582 hasAuthorship W2564026582A5039762705 @default.
• W2564026582 hasAuthorship W2564026582A5039994927 @default.
• W2564026582 hasAuthorship W2564026582A5041163911 @default.
• W2564026582 hasAuthorship W2564026582A5048714300 @default.
• W2564026582 hasAuthorship W2564026582A5052246323 @default.
• W2564026582 hasAuthorship W2564026582A5077253651 @default.
• W2564026582 hasAuthorship W2564026582A5080576155 @default.
• W2564026582 hasConcept C104317684 @default.
• W2564026582 hasConcept C10590036 @default.
• W2564026582 hasConcept C113968399 @default.
• W2564026582 hasConcept C121608353 @default.
• W2564026582 hasConcept C126322002 @default.
• W2564026582 hasConcept C132917006 @default.
• W2564026582 hasConcept C141231307 @default.
• W2564026582 hasConcept C143998085 @default.
• W2564026582 hasConcept C16671776 @default.
• W2564026582 hasConcept C2778559949 @default.
• W2564026582 hasConcept C2779338263 @default.
• W2564026582 hasConcept C2780265364 @default.
• W2564026582 hasConcept C2780653079 @default.
• W2564026582 hasConcept C2780790343 @default.
• W2564026582 hasConcept C2781187634 @default.
• W2564026582 hasConcept C501734568 @default.
• W2564026582 hasConcept C502942594 @default.
• W2564026582 hasConcept C526805850 @default.
• W2564026582 hasConcept C54355233 @default.
• W2564026582 hasConcept C71924100 @default.
• W2564026582 hasConcept C86803240 @default.
• W2564026582 hasConceptScore W2564026582C104317684 @default.
• W2564026582 hasConceptScore W2564026582C10590036 @default.
• W2564026582 hasConceptScore W2564026582C113968399 @default.
• W2564026582 hasConceptScore W2564026582C121608353 @default.
• W2564026582 hasConceptScore W2564026582C126322002 @default.
• W2564026582 hasConceptScore W2564026582C132917006 @default.
• W2564026582 hasConceptScore W2564026582C141231307 @default.
• W2564026582 hasConceptScore W2564026582C143998085 @default.
• W2564026582 hasConceptScore W2564026582C16671776 @default.
• W2564026582 hasConceptScore W2564026582C2778559949 @default.
• W2564026582 hasConceptScore W2564026582C2779338263 @default.
• W2564026582 hasConceptScore W2564026582C2780265364 @default.
• W2564026582 hasConceptScore W2564026582C2780653079 @default.
• W2564026582 hasConceptScore W2564026582C2780790343 @default.
• W2564026582 hasConceptScore W2564026582C2781187634 @default.
• W2564026582 hasConceptScore W2564026582C501734568 @default.
• W2564026582 hasConceptScore W2564026582C502942594 @default.
• W2564026582 hasConceptScore W2564026582C526805850 @default.
• W2564026582 hasConceptScore W2564026582C54355233 @default.
• W2564026582 hasConceptScore W2564026582C71924100 @default.
• W2564026582 hasConceptScore W2564026582C86803240 @default.
• W2564026582 hasLocation W25640265821 @default.
• W2564026582 hasOpenAccess W2564026582 @default.
• W2564026582 hasPrimaryLocation W25640265821 @default.
• W2564026582 hasRelatedWork W1015385261 @default.
• W2564026582 hasRelatedWork W1973661900 @default.
• W2564026582 hasRelatedWork W2275283368 @default.
• W2564026582 hasRelatedWork W2530920543 @default.
• W2564026582 hasRelatedWork W2546061993 @default.
• W2564026582 hasRelatedWork W2549700760 @default.
• W2564026582 hasRelatedWork W2553920645 @default.
• W2564026582 hasRelatedWork W2557353056 @default.
• W2564026582 hasRelatedWork W2570395244 @default.
• W2564026582 hasRelatedWork W2588014963 @default.
• W2564026582 hasRelatedWork W2589472232 @default.
• W2564026582 hasRelatedWork W2594001221 @default.
• W2564026582 hasRelatedWork W2594580851 @default.
• W2564026582 hasRelatedWork W2609293428 @default.
• W2564026582 hasRelatedWork W2900881192 @default.
• W2564026582 hasRelatedWork W2979740098 @default.
• W2564026582 hasRelatedWork W3010233098 @default.
• W2564026582 hasRelatedWork W3037474453 @default.
• W2564026582 hasRelatedWork W3193063011 @default.
• W2564026582 hasRelatedWork W69839775 @default.
• W2564026582 isParatext "false" @default.
• W2564026582 isRetracted "false" @default.

• next