Deltex-1 mutations predict poor survival in diffuse large B-cell lymphoma

Meriranta, Leo; Pasanen, Annika; Louhimo, Riku; Cervera, Alejandra; Alkodsi, Amjad; Autio, Matias; Taskinen, M.-R.; Rantanen, Ville; Karjalainen-Lindsberg, Marja Liisa; Holte, Harald; Delabie, Jan; Lehtonen, Rainer; Hautaniemi, Sampsa; Leppä, Sirpa

doi:10.3324/haematol.2016.157495

Cited by 23 publications

(18 citation statements)

References 14 publications

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“…All of the mutations (12 non-synonymous mutations in seven patients), except two splicing mutations, were located in exon 1 (S4 Table), affecting the WWE1 domain of the protein, and have been previously demonstrated to weaken DTX1 function as a negative regulator of Notch [38]. DTX1 mutations are associated with shorter time to progression and OS in DLBLC [39]. NOTCH2, regulated by DTX1 protein, has been found recurrently mutated in several types of lymphoma, including splenic marginal zone lymphoma [40,41], DLBCL [31,32,42] and FL [30,43].…”

Section: Discussionmentioning

confidence: 99%

Unraveling transformation of follicular lymphoma to diffuse large B-cell lymphoma

et al. 2019

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Follicular lymphoma (FL) is an indolent but largely incurable disease. Some patients suffer histological transformation to a more aggressive subtype with poorer prognosis. This study aimed to improve our understanding of the genetics underlying FL histological transformation, and to identify genetic drivers or promoters of the transformation by elucidating the differences between FL samples from patients who did and did not transform. We conducted targeted massive parallel sequencing of 22 pre-transformed FL/transformed diffuse large B-cell lymphoma pairs and 20 diagnostic samples from non-transformed FL patients. Additionally, 22 matched samples from 11 transformed FL patients (pre-transformed FL and diffuse large B-cell lymphoma) and 9 non-transformed FLs were studied for copy number variation using SNP arrays. We identified recurrently mutated genes that were enriched at transformation, most notably LRP1B , GNA13 and POU2AF1 , which have roles in B-cell differentiation, GC architecture and migration. Mutations in POU2AF1 might be associated with lower levels of expression, were more frequent in transformed FLs, and seemed to be specific to transformed- compared with de novo- diffuse large B-cell lymphomas. Pre-transformed FLs carried more mutations per sample and had greater subclonal heterogeneity than non-transformed FLs. Finally, we identified four mutated genes in FL samples that differed between patients who did and did not transform: NOTCH2 , DTX1 , UBE2A and HIST1H1E . The presence of mutations in these genes was associated with shorter time to transformation when mutated in the FL biopsies. This information might be useful for identifying patients at higher risk of transformation.

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Section: Discussionmentioning

confidence: 99%

Unraveling transformation of follicular lymphoma to diffuse large B-cell lymphoma

et al. 2019

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“…23,24 Recently, poor prognosis of patients with diffuse large B-cell lymphoma with DTX1 mutations has been reported. 25 rs1732786A > G is located in the promoter region of DTX1, and our in vitro functional study showed that rs1732786A > G was associated with increased promoter activity. In our previous study, the variant also increased DTX1 mRNA expression in surgically resected NSCLC.…”

Section: Discussionmentioning

confidence: 59%

Effect of genetic variation in Notch regulator DTX1 on SCLC prognosis compared with the effect on NSCLC prongosis

et al. 2020

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Deltex‐1 (DTX1) is a negative regulator of the Notch signaling pathway. Here, we investigated the clinical effect of DTX1 rs1732786A > G, which is associated with better prognosis in patients with early‐stage non‐small cell lung cancer (NSCLC), in 261 patients with small cell lung cancer (SCLC). DTX1 rs1732786A > G was associated with a significantly worse chemotherapy response and lower overall survival in the codominant model (odds ratio = 0.42, 95% confidence interval [CI]: 0.26–0.66, P = 2 × 10−4; hazard ratio = 1.47, 95% CI: 1.17–1.84, P = 0.001, respectively). An in vitro luciferase assay was performed, and the 1732786G allele demonstrated significantly higher promoter activity than the 1732786A allele (P = 2 × 10−7). In summary, DTX1 rs1732786A > G was associated with poor prognosis in patients with SCLC as opposed to patients with NSCLC. Key points Significant findings of the study DTX1 rs1732786A > G was associated with better prognosis in patients with early‐stage non‐small cell lung cancer (NSCLC) in our previous study. What this study adds DTX1 rs1732786A > G was associated with a significantly worse chemotherapy response and lower overall survival in small cell lung cancer (SCLC).

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“…Patients of GBM with a lower level of DTX1 survived longer and had better prognoses 23 . In diffuse large B-cell lymphoma (DLBCL), mutations in DTX1 gene could be discovered to impair its original effects, nearly 65% of which were found in the WWE1-domain 24 . In gastric cancer, DTX1 was reported specifically down-regulated and promoted cellular FLICE inhibitory protein (c-FLIP), as its E3 ligase substrate, to degrade through the endosome-lysosomal pathway 25 .…”

Section: Discussionmentioning

confidence: 99%

Deltex3 inhibits Epithelial Mesenchymal Transition in Papillary Thyroid Carcinoma via promoting ubiquitination of XRCC5 to regulate the AKT signal pathway

Wang¹,

Huang²,

Liu³

et al. 2021

J. Cancer

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Deltex-1 mutations predict poor survival in diffuse large B-cell lymphoma

Cited by 23 publications

References 14 publications

Unraveling transformation of follicular lymphoma to diffuse large B-cell lymphoma

Unraveling transformation of follicular lymphoma to diffuse large B-cell lymphoma

Effect of genetic variation in Notch regulator DTX1 on SCLC prognosis compared with the effect on NSCLC prongosis

Deltex3 inhibits Epithelial Mesenchymal Transition in Papillary Thyroid Carcinoma via promoting ubiquitination of XRCC5 to regulate the AKT signal pathway

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