Predictive values of mutational variant allele frequency in overall survival and leukemic progression of myelodysplastic syndromes

Jiang, Lingxu; Li, Ye; Ma, Liya; Ren, Yanling; Zhou, Xinping; Chen, Mei; Xu, Gaixiang; Yang, Haiyang; Lu, Chenxi; Luo, Yingwan; Zhu, Shuhua; Wang, Lu; Shen, Chuying; Yang, Wenli; Zhang, Qi; Wang, Yuxia; Lang, Wei; Han, Yineng; Jin, Jie; Tong, Hongyan

doi:10.1007/s00432-021-03905-y

Cited by 11 publications

(27 citation statements)

References 32 publications

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“…TP53 VAF could stratify distinct prognostic groups independent of clinical prognostic scoring systems. 16,18,19,47 However, the cutoff values of mutant TP53 VAF that could discriminate outcomes varied among studies. A meta-analysis including 11 studies suggested a threshold of 20% as a rough line between high and low clone burden and 40% as a cutoff point to guide treatment.…”

Section: Discussionmentioning

confidence: 99%

Effect of mutation allele frequency on the risk stratification of myelodysplastic syndrome patients

et al. 2022

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Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal myeloid malignancies. Though several recurrent mutations are closely correlated with clinical outcomes, data concerning the association between mutation variant allele frequencies (VAF) and prognosis are limited. In this study, we performed comprehensive VAF analyses of relevant myeloid-malignancy related mutations in 698 MDS patients and correlated the results with their prognosis. Mutation VAF in DNMT3A, TET2, ASXL1, EZH2, SETBP1, BCOR, SFSF2, ZRSR2, and TP53 mutations correlated with outcomes.In multivariable analysis, DNMT3A and ZRSR2 mutations with high VAF and mutant IDH2, CBL, U2AF1, and TP53 were independent poor prognostic factors for overall survival. A substantial portion of patients in each revised International Prognostic Scoring System (IPSS-R) risk group could be adjusted to different prognostic groups based on the integrated VAF and mutational profiles. Patients with these unfavorable mutations in each IPSS-R risk subgroup had survivals worse than other patients of the same risk but similar to those in the next higher-risk subgroup. Furthermore, patients harboring U2AF1 mutation might benefit from hypomethylating agents. This study demonstrated the critical role of VAF of mutations for risk stratification in MDS patients and may be incorporated in novel scoring systems.

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Section: Discussionmentioning

confidence: 99%

Effect of mutation allele frequency on the risk stratification of myelodysplastic syndrome patients

et al. 2022

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Section: Introductionmentioning

confidence: 99%

“…Given that radiation therapy (RT) has remained the mainstay in adjuvant therapy over the last 3 decades, the identification of molecular subtypes that could benefit from (de)escalation will be paramount to improving outcomes. 7,[17][18][19] Furthermore, the allelic frequency of TP53 mutations has been demonstrated to negatively impact clinical outcomes in myelodysplastic disorders 15,[20][21][22][23] and the development of sCNA alterations 14 .The fundamental molecular and biologic rationale driving discrepant clinical outcomes in EC is lacking. Given this, we set out to determine the association between TP53 VAF and clinical outcomes in EC, as well as the direct therapeutic impact of TP53 alterations using cell lines.…”

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confidence: 99%

Leveraging the p53 signaling pathway as a radio-sensitization strategy in endometrial cancer

Vargas

Petty

Yard³

et al. 2022

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Endometrial cancer (EC) is the most common type of gynecologic malignancy in the United States, with over 65,950 new cases expected in 2022. Approximately 80% of cancer-related mortalities can be attributed to high-grade EC. Despite our ability to identify different biologic clusters of EC, we have yet to understand the functional and therapeutic impact of the key genomic alterations associated with poor prognosis EC and exploit this knowledge for therapeutic benefit. Given this, we set out to determine if and how common TP53 alterations found in high-grade ECs impact radiotherapy response, and if manipulation of this signaling pathway could be utilized for therapeutic intervention. Our work demonstrates that p53 signaling plays a significant role in radiotherapy response for EC and that leveraging this genomic data may allow us to exploit this pathway as a viable therapeutic target.

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“…With the use of next generation sequencing (NGS) technologies, 70–90% of MDS patients were detected with one or more genetic mutations 20‐24 . Mutations were found to be associated with clinical phenotypes and prognosis in MDS patients 25 .…”

Section: Introductionmentioning

confidence: 99%

“…With the use of next generation sequencing (NGS) technologies, 70-90% of MDS patients were detected with one or more genetic mutations. [20][21][22][23][24] Mutations were found to be associated with clinical phenotypes and prognosis in MDS patients. 25 The correlation between aberrant karyotypes and genetic mutations has been described previously.…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of cytogenetic and molecular genetic abnormalities in 634 Chinese patients with myelodysplastic syndromes

et al. 2021

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Predictive values of mutational variant allele frequency in overall survival and leukemic progression of myelodysplastic syndromes

Cited by 11 publications

References 32 publications

Effect of mutation allele frequency on the risk stratification of myelodysplastic syndrome patients

Effect of mutation allele frequency on the risk stratification of myelodysplastic syndrome patients

Leveraging the p53 signaling pathway as a radio-sensitization strategy in endometrial cancer

Clinical significance of cytogenetic and molecular genetic abnormalities in 634 Chinese patients with myelodysplastic syndromes

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