Genomic data integration in chronic lymphocytic leukemia

Fernández-Martínez, Juan Luis; deAndrés-Galiana, Enrique J.; Sonis, Stephen T.

doi:10.1002/jgm.2936

Cited by 23 publications

(22 citation statements)

References 63 publications

(108 reference statements)

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“…In a previous research [20] we have shown that 4 genes (IGHG1, MYBL1, NRIP1 and RGS13) belong to the intersection of IgHV, NOTCH1 and SF3B1 mutations and that IL-4-mediated signaling events pathway seems to be involved as a common mechanism for disease progression. This analysis also highlights the importance of IGHG1 and RGS13 in the disease progression.…”

Section: Page 7 Ofmentioning

confidence: 92%

“…The methodology tries to determine the shortest lists of most discriminatory genes that predict the NOP16 mutation and is described by Fernández-Martínez et al [20] and De Andrés-Galiana et al [22][23][24]. This classification problem is naturally unbalanced due to the low number of patients that show the NOP16 mutation, and the classifier has to take this feature into account.…”

Section: Methodsmentioning

confidence: 99%

“…We have used the Fisher's Ratio and Fold Change to rank the genes according to their discriminatory power [20,[22][23][24]. These gene-ranking methods and particularly Fisher's ratio turned to be very robust against different kind of noise [24].…”

Section: Methodsmentioning

confidence: 99%

“…NOP16 seems to be an independent factor for CLL development from NOTCH1 and SF3B1 mutations. Previous work has shown that these mutations (NOTCH1 and SF3B1) are independent and jointly affecting the immunologic system (IL-4-mediated signaling events pathway) [20].…”

Section: Data Descriptionmentioning

confidence: 99%

“…Therefore, the main CLL mutations should share some common mechanisms that are responsible for CLL development and bad prognosis. A retrospective analysis to understand the effect the main mutations (IgHV, NOTCH1 and SF3B1) in gene expression and the existing relationships between them have been recently performed using the same dataset [20].…”

Section: Introductionmentioning

confidence: 99%

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The Effect of NOP16 Mutation in Chronic Lymphocytic Leukemia

Jl¹,

Ej²,

Cernea³

2017

J Mol Genet Med

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NOP16 was the third most important mutation (6.84%) in a reduced-size cohort of 117 patients with Chronic Lymphocytic Leukemia (CLL) whose most recurrent mutations were NOTCH1 (9.4%) and SF3B1 (8.55%). In this paper we analyzed the effect of the NOP16 mutation in gene expression. The NOP16 mutation was predicted with 100% accuracy using a small-scale signature formed by the 26 genes with the highest Fisher's Ratio. SLC39A4 (ZIP4) and WARS are the most discriminatory genes of this mutation providing a predictive accuracy of 97.4%. The Fold Change analysis also confirmed a very important role of the light (IGKV3D-11, IGKC and IGLJ3) and heavy (IGHG1) chain immunoglobulins, SOX11, CCND1 and CHL1. This analysis also highlights the importance of several mechanisms such as the ZIP4-related apoptosis, the SOX11-CCND1 over expression relationship observed in mantle cell-lymphoma, and CHL1 down regulation and over expression of the midkine-neurite growth-promoting factor that enhances the angiogenic and proliferative activities of cancer cells in different types of solid cancers. Besides, the holdout stability analysis has shown the importance of Signaling Events of B Cell Receptor (BCR), P53 signaling, Infectious disease, and TGF-beta Receptor Signaling. The integration of the NOP16 mutation with the IgHV, NOTCH1 and SF3B1 mutations, that were previously analyzed, confirmed that these mutations only share two high discriminatory genes: IGHG1 and RGS13. These genes are involved in different mechanisms concerning signaling and the immunological system. This analysis opens novel working hypothesis for CLL treatment and prognosis.

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Section: Page 7 Ofmentioning

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Data Descriptionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Effect of NOP16 Mutation in Chronic Lymphocytic Leukemia

Jl¹,

Ej²,

Cernea³

2017

J Mol Genet Med

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NOTCH1 mutation and its prognostic significance in Chinese chronic lymphocytic leukemia: a retrospective study of 317 cases

et al. 2018

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The proto‐oncogene NOTCH1 is frequently mutated in around 10% of patients with chronic lymphocytic leukemia (CLL). This study analyzed NOTCH1 mutation status of 317 Chinese patients with CLL by Sanger sequencing. The frequencies of NOTCH1 mutation in the PEST (proline (P), glutamic acid (E), serine (S), threonine (T)‐rich protein sequence) domain and the 3′ untranslated regions (UTR) were 8.2% and 0.9%, with the most frequent mutation being c.7541_7542delCT and c.*371A>G, respectively. Clinical and biological associations were determined including NOTCH1 mutations with advanced stage (Binet stage, P = 0.010), unmutated immunoglobulin heavy‐chain variable region (IGHV) gene (P < 0.001) and trisomy 12 (+12) (P = 0.014). NOTCH1‐mutated patients had lower CD20 expression intensity than NOTCH1‐unmutated patients (P = 0.029). In addition, NOTCH1‐mutated patients had shorter overall survival (OS) (P = 0.002) and treatment‐free survival (TFS) (P = 0.002) than NOTCH1‐unmutated patients, especially for patients with NOTCH1 c.7541_7542delCT and/or c.*371A>G mutations. Patients with both mutated NOTCH1 and unmutated IGHV had shorter OS (P < 0.001) and TFS (P < 0.001) than those with unmutated NOTCH1 or mutated IGHV. These data provide a comprehensive view of the clinical relevance and prognostic impact of NOTCH1 mutations on Chinese patients with CLL.

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Ribosomal protein L32 enhances hepatocellular carcinoma progression

Hou

Jiang

et al. 2023

Cancer Medicine

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Purpose The underlying mechanisms of hepatocellular carcinoma (HCC) have not been fully investigated, and effective biomarkers for HCC are still needed to be explored. Therefore, our study sought to thoroughly examine the clinical significance and biological functions of the ribosomal protein L32 (RPL32) in HCC by coupling bioinformatic methods with experimental analysis. Methods To determine the clinical significance of RPL32, bioinformatic analyses were performed to examine RPL32 expression in HCC patient samples and to correlate RPL32 expression and HCC patient survival rates, genetic alterations, and immune cell infiltration. Cell counting kit‐8 assays, colony formation, flow cytometry, and transwell assays were performed to examine the effects of RPL32 on HCC cell proliferation, apoptosis, migration, and invasion in HCC cell lines (SMMC‐7721 and SK‐HEP‐1) where RPL32 was silenced using small interfering ribonucleic acid. Results In the current study, we show that RPL32 was highly expressed in HCC samples. Moreover, high levels of RPL32 were associated with unfavorable outcomes in patients with HCC. Promoter methylation and copy number variation of RPL32 were associated with RPL32 mRNA expression. Results from the RPL32 silencing experiments indicated that the proliferation, apoptosis, migration, and invasion of SMMC‐7721 and SK‐HEP‐1 cells were attenuated upon RPL32 depletion. Conclusion RPL32 correlates with a favorable prognosis in patients with HCC and promotes the survival, migration, and invasion of HCC cells.

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Genomic data integration in chronic lymphocytic leukemia

Abstract: This retrospective analysis served to provide a deeper understanding of the effects of the different mutations in CLL disease progression, with the expectation that these findings will be clinically applied in the near future to the development of new drugs.

Cited by 23 publications

References 63 publications

The Effect of NOP16 Mutation in Chronic Lymphocytic Leukemia

The Effect of NOP16 Mutation in Chronic Lymphocytic Leukemia

NOTCH1 mutation and its prognostic significance in Chinese chronic lymphocytic leukemia: a retrospective study of 317 cases

Ribosomal protein L32 enhances hepatocellular carcinoma progression

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