Risk Stratification Using a Novel Genetic Classifier Including<i>PLEKHS1</i>Promoter Mutations for Differentiated Thyroid Cancer with Distant Metastasis

Jung, Chan Kwon; Jung, Seung‐Hyun; Jeon, Sora; Jeong, Young Mun; Kim, Yourha; Lee, Sohee; Bae, Ja Seong; Chung, Yeun‐Jun

doi:10.1089/thy.2019.0459

Cited by 27 publications

(18 citation statements)

References 34 publications

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“…Forty-six remaining studies were retrieved for assessment, and a flow chart showed the process of literature retrieval (Figure 1). Of 13 eligible articles, 12 were retrospective studies, and one study from China was prospective (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Two appropriate reports were included, although they were conference abstracts.…”

Section: Search Results and Characteristics Of Patientsmentioning

confidence: 99%

Clinical, Pathological, and Molecular Characteristics Correlating to the Occurrence of Radioiodine Refractory Differentiated Thyroid Carcinoma: A Systematic Review and Meta-Analysis

Luo

Jiang

et al. 2020

Front. Oncol.

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Background: Recently, radioiodine refractory differentiated thyroid cancer (RR-DTC) has received increasing attention due to its poor prognosis. The roles of clinical, pathological, and molecular features in the development of RR-DTC remain controversial and require additional investigation. This study aimed to evaluate the association between these risk factors and the occurrence of RR-DTC. Methods: We performed a systematic search for relevant literature following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) in PubMed, EMBASE, Medline, SCOPUS, and Web of Science up to the July 15, 2020. Observational studies that investigated the risk factors for RR-DTC were included. Fixed-or random-effects models were used to calculate pooled odds ratios (ORs) or mean differences (MD) with corresponding 95% confidence intervals. Results: We included 13 eligible studies incorporating 1,431 cases, of which 603 were patients with RR-DTC. The pooled analysis indicated that four parameters significantly increased the risk of RR-DTC: extrathyroidal extension (ETE) (OR: 2.28, 95% CI: 1.43-3.64, I 2 = 14%), BRAF V600E mutation (OR: 3.60, 95% CI: 1.74-7.46, I 2 = 69%), TERT promoter mutation (OR: 9.84, 95% CI: 3.60-26.89, I 2 = 61%) and high-risk histological subtype (OR: 1.94, 95% CI: 1.15-3.27, I 2 = 15%), including tall cell variant papillary thyroid carcinoma (PTC), sclerosing diffuse PTC, hobnail variant PTC, follicular thyroid carcinoma (FTC) (including Hürthle cell), and poorly differentiated thyroid carcinoma (PDTC). However, there was no statistical significance regarding sex, age, tumor size, multifocality, or lateral lymph node metastasis. Subgroup and sensitivity analyses were conducted to further confirm the robustness of the results. Luo et al. Predictors of Radioiodine Refractory PTC Conclusions: Histological subtype, ETE, BRAF V600E mutation, and TERT promoter mutation could be considered clinicopathological factors and biomarkers. They could assist in risk stratification, prognostic prediction, and individual therapy options for RR-DTC.

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Section: Search Results and Characteristics Of Patientsmentioning

confidence: 99%

Clinical, Pathological, and Molecular Characteristics Correlating to the Occurrence of Radioiodine Refractory Differentiated Thyroid Carcinoma: A Systematic Review and Meta-Analysis

Luo

Jiang

et al. 2020

Front. Oncol.

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“…For example, SRARP (Steroid Receptor Associated And Regulated Protein) is a protein coding gene, which could function as a tumor suppressors and predict clinical outcome in malignancies (36). PLEKHS1 (pleckstrin homology domain containing S1) promoter mutations are a poor prognosis genetic marker for thyroid cancer (37).…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Gene Signature for Prediction of Relapse in Stage I Testicular Germ Cell Tumors

et al. 2020

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Background: Testicular germ cell tumors (TGCTs) are commonly diagnosed tumors in young men. However, a satisfactory approach to predict relapse of stage I TGCTs is still lacking. Therefore, this study aimed to develop a robust risk score model for stage I TGCTs. Method: RNA-sequence data of stage I TGCTs and normal testis samples were downloaded and analyzed to identify different expression genes. Gene-based prognostic model was constructed in The Cancer Genome Atlas (TCGA) using least absolute shrinkage and selection operator (LASSO) regression analysis and validated in GSE99420 dataset. Potential biological functions of the genes in prognostic model were determined via Gene Set Enrichment Analysis (GSEA) between high-risk and low-risk patients. Results: A total of 9,391 differentially expressed genes and 84 prognosis-related genes were identified. An eight-gene-based risk score model was constructed to divide patients into high or low risk of relapse. The low-risk patients had a significantly better relapse-free survival (RFS) than high-risk patients in both training and validation cohorts (HR = 0.129, 95% CI = 0.059-0.284, P < 0.001; HR = 0.277, 95% CI = 0.116-0.661, P = 0.004, respectively). The area under the receiver operating characteristic curve (AUC) values at 5 years was 0.805 and 0.724 in the training and validation cohorts, respectively. Functional enrichment analyses showed that DNA replication, ribosome, cell cycle, and TGF-beta signaling pathway may contribute to the relapse process. Conclusion: In summary, our analysis provided a novel eight-gene signature that could predict RFS in stage I TGCT patients.

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“…Our analysis of the mutation burden within luminal ER+PR+ breast cancer cis-regulatory elements yielded only seven significant hits. Across both the ICGC-US and -EU cohorts, we found significant enrichment of mutations in the PLEKHS1 promoter that is likely a result of APOBEC DNA-editing activity 1 , however, this region is also known as a genetic marker of aggressiveness for differentiated thyroid carcinomas 53 . Although significant, our results show that the hunt for cancer drivers within individual cis-regulatory elements is limiting at best, resulting in the few observed recurrently mutated individual cis-regulatory elements.…”

Section: Discussionmentioning

confidence: 85%

Non-coding mutations reveal cancer driver cistromes in luminal breast cancer

Quevedo

Hawley

et al. 2021

Preprint

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Whole-genome sequencing of primary breast tumors enabled the identification of cancer driver genes and non-coding cancer driver plexuses from somatic mutations. However, differentiating driver and passenger events among non-coding genetic variants remains a challenge to understand the etiology of cancer and inform the delivery of personalized cancer medicine. Herein, we reveal an enrichment of non-coding mutations in cis-regulatory elements that cover a subset of transcription factors linked to tumor progression in luminal breast cancers. Using a cohort of 26 primary luminal ER+PR+ breast tumors, we compiled a catalogue of ~100,000 unique cis-regulatory elements from ATACseq data. Integrating this catalogue with somatic mutations from 350 publicly available breast tumor whole genomes, we identified four recurrently mutated individual cis-regulatory elements. By then partitioning the non-coding genome into cistromes, defined as the sum of binding sites for a transcription factor, we uncovered cancer driver cistromes for ten transcription factors in luminal breast cancer, namely CTCF, ELF1, ESR1, FOSL2, FOXA1, FOXM1 GATA3, JUND, TFAP2A, and TFAP2C in luminal breast cancer. Nine of these ten transcription factors were shown to be essential for growth in breast cancer, with four exclusive to the luminal subtype. Collectively, we present a strategy to find cancer driver cistromes relying on quantifying the enrichment of non-coding mutations over cis-regulatory elements concatenated into a functional unit drawn from an accessible chromatin catalogue derived from primary cancer tissues.

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Risk Stratification Using a Novel Genetic Classifier IncludingPLEKHS1Promoter Mutations for Differentiated Thyroid Cancer with Distant Metastasis

Cited by 27 publications

References 34 publications

Clinical, Pathological, and Molecular Characteristics Correlating to the Occurrence of Radioiodine Refractory Differentiated Thyroid Carcinoma: A Systematic Review and Meta-Analysis

Clinical, Pathological, and Molecular Characteristics Correlating to the Occurrence of Radioiodine Refractory Differentiated Thyroid Carcinoma: A Systematic Review and Meta-Analysis

Development and Validation of a Gene Signature for Prediction of Relapse in Stage I Testicular Germ Cell Tumors

Non-coding mutations reveal cancer driver cistromes in luminal breast cancer

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