|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
This previously unidentified, recurrent mutation in U2AF1 implicates altered pre-mRNA splicing as a potential mechanism for MDS pathogenesis.
|
22158538 |
2011 |
|
Leukemia, Myelocytic, Acute
|
0.470 |
AlteredExpression
|
disease |
BEFREE |
Collectively, mutations in U2AF1 induce expression of therapeutically targetable 'active' IRAK4 isoforms and provide a genetic link to activation of chronic innate immune signalling in MDS and AML.
|
31011167 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.470 |
GeneticVariation
|
disease |
BEFREE |
The results showed that U2AF1 mutant had an adverse prognostic impact on OS (HR = 1.84, 95% CI: 1.45-2.33, P < 0.00001) and AML transformation (HR = 2.47, 95% CI: 1.50-4.06, P = 0.0004).
|
31754743 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.470 |
Biomarker
|
disease |
BEFREE |
Using RNA-Seq data from 182 lung adenocarcinomas and 167 acute myeloid leukemias (AML), in which U2AF1 is somatically mutated in 3-4% of cases, we identified 131 and 369 splicing alterations, respectively, that were significantly associated with U2AF1 mutation.
|
24498085 |
2014 |
|
Leukemia, Myelocytic, Acute
|
0.470 |
GeneticVariation
|
disease |
BEFREE |
Integration with human RNA-seq datasets determined that common mutant U2AF1-induced splicing alterations are enriched in RNA processing genes, ribosomal genes, and recurrently mutated MDS and acute myeloid leukemia-associated genes.
|
25965570 |
2015 |
|
Leukemia, Myelocytic, Acute
|
0.470 |
GeneticVariation
|
disease |
BEFREE |
Our data show that U2AF1 mutation is a recurrent event at a low frequency in AML and MDS.
|
23029227 |
2012 |
|
Leukemia, Myelocytic, Acute
|
0.470 |
GeneticVariation
|
disease |
BEFREE |
Over the past few years, large-scale genomic studies of patients with myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) have unveiled recurrent somatic mutations in genes involved in epigenetic regulation (DNMT3A, IDH1/2, TET2, ASXL1, EZH2 and MLL) and the spliceosomal machinery (SF3B1, U2AF1, SRSF2, ZRSR2, SF3A1, PRPF40B, U2AF2, and SF1).
|
23645565 |
2013 |
|
Leukemia, Myelocytic, Acute
|
0.470 |
Biomarker
|
disease |
BEFREE |
Results confirm high frequencies of RAS and other activated signaling mutations (10/12 AMLs) and identify new recurrent mutations in splicing factors (5/12 AMLs in SF3B1 and 2/12 AMLs in U2AF1), IKZF1 (3/12 AMLs), and TP53 (3/12 AMLs).
|
25331116 |
2015 |
|
Chronic Lymphocytic Leukemia
|
0.310 |
Biomarker
|
disease |
BEFREE |
U2AF1 is frequently mutated in myeloid hematopoietic malignancies, especially in myelodysplastic syndrome (MDS), and SF3B1 is frequently mutated in both MDS and chronic lymphocytic leukemia (CLL).
|
22200771 |
2011 |
|
Adenocarcinoma of lung (disorder)
|
0.130 |
GeneticVariation
|
disease |
BEFREE |
Finally, we show that lung adenocarcinoma cell lines bearing U2AF1 mutations do not require the mutant protein for growth in vitro or in vivo.
|
27776121 |
2016 |
|
Adenocarcinoma of lung (disorder)
|
0.130 |
GeneticVariation
|
disease |
BEFREE |
Taken together, our results suggest a mechanistic interaction between mutant U2AF1 and ROS1 in LUAD.
|
31836708 |
2019 |
|
Adenocarcinoma of lung (disorder)
|
0.130 |
Biomarker
|
disease |
BEFREE |
Using RNA-Seq data from 182 lung adenocarcinomas and 167 acute myeloid leukemias (AML), in which U2AF1 is somatically mutated in 3-4% of cases, we identified 131 and 369 splicing alterations, respectively, that were significantly associated with U2AF1 mutation.
|
24498085 |
2014 |
|
Malignant Neoplasms
|
0.070 |
GeneticVariation
|
group |
BEFREE |
A single missense point mutation (S34F) in the essential splicing factor U2AF1 which occurs in human cancers perturbs this kinetic balance and defers splicing to occur entirely post-release.
|
25271374 |
2014 |
|
Malignant Neoplasms
|
0.070 |
GeneticVariation
|
group |
BEFREE |
Although recurrent somatic mutations in the splicing factor U2AF1 (also known as U2AF35) have been identified in multiple cancer types, the effects of these mutations on the cancer transcriptome have yet to be fully elucidated.
|
24498085 |
2014 |
|
Malignant Neoplasms
|
0.070 |
GeneticVariation
|
group |
BEFREE |
SRSF2, SF3B1, and U2AF35 (U2AF1) are the three most frequent genes involved with spliceosome mutations in myeloid malignancies.
|
23335386 |
2013 |
|
Malignant Neoplasms
|
0.070 |
GeneticVariation
|
group |
BEFREE |
TP53 and U2AF1 mutations have been implicated in other myelomonocytic malignancies and we hypothesized that mutations in these genes may cosegregate in LCH patients according to BRAF mutation status.
|
29649018 |
2018 |
|
Malignant Neoplasms
|
0.070 |
GeneticVariation
|
group |
BEFREE |
Taken together, our results demonstrate that ATR may represent a novel therapeutic target in patients with MDS carrying the U2AF1(S34F) mutation and potentially other malignancies harboring spliceosome mutations.<b>Significance:</b> This study provides preclinical evidence that patients with MDS or other myeloid malignancies driven by spliceosome mutations may benefit from ATR inhibition to exploit the R loop-associated vulnerability induced by perturbations in splicing.<i>Cancer Res; 78(18); 5363-74.©2018 AACR</i>.
|
30054334 |
2018 |
|
Malignant Neoplasms
|
0.070 |
GeneticVariation
|
group |
BEFREE |
The cancer-associated U2AF35 470A>G (Q157R) mutation creates an in-frame alternative 5' splice site that impacts splicing regulation in Q157R patients.
|
28893951 |
2017 |
|
Malignant Neoplasms
|
0.070 |
GeneticVariation
|
group |
BEFREE |
U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies.
|
31011167 |
2019 |
|
Neoplasms
|
0.050 |
GeneticVariation
|
group |
BEFREE |
Using an integrative approach combining genomic and transcriptomic data, we molecularly characterized 30 pediatric T-ALLs and identified common recurrent T-ALL targets such as FBXW7, JAK1, JAK3, PHF6, KDM6A and NOTCH1 as well as novel candidate T-ALL driver mutations including the p.R35L missense mutation in splicesome factor U2AF1 found in 3 patients and loss of function mutations in the X-linked tumor suppressor genes MED12 (frameshit mutation p.V167fs, splice site mutation g.chrX:70339329T>C, missense mutation p.R1989H) and USP9X (nonsense mutation p.Q117*).
|
27602765 |
2016 |
|
Neoplasms
|
0.050 |
GeneticVariation
|
group |
BEFREE |
These novel observations support the hypothesis that U2AF1 mutations play a significant role in myeloid leukemogenesis due to selective missplicing of tumor-associated genes.
|
23775717 |
2013 |
|
Neoplasms
|
0.050 |
GeneticVariation
|
group |
BEFREE |
We also report a novel finding-our study reveals a high frequency of U2AF1 mutations at codon Q157 associated with CSF3R mutant myeloid neoplasms.
|
26637732 |
2015 |
|
Neoplasms
|
0.050 |
GeneticVariation
|
group |
BEFREE |
Our results provide mechanistic explanations of the magnitude of splicing changes observed in U2AF1-mutant cells and why tumors harboring U2AF1 mutations always retain an expressed copy of the wild-type allele.
|
27776121 |
2016 |
|
Neoplasms
|
0.050 |
GeneticVariation
|
group |
BEFREE |
In this study, we analyzed the frequency and clinical impact of U2AF1 mutations in a cohort of 452 Chinese patients with myeloid neoplasms.
|
23029227 |
2012 |
|
Leukemia, Myelomonocytic, Chronic
|
0.030 |
GeneticVariation
|
disease |
BEFREE |
In this study of 226 patients with chronic myelomonocytic leukemia (CMML), mutational frequencies were 40% for SRSF2 (all affecting P95), 6% for SF3B1 (primarily K700E) and 9% for U2AF35 (mostly S34F and Q157P/R).
|
23335386 |
2013 |