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Founder Mutations for Early Onset Melanoma as Revealed by Whole Exome Sequencing Suggests That This is Not Associated with the Increasing Incidence of Melanoma in Poland
Tadeusz Dębniak, Rodney J Scott, Rodney A Lea, Bohdan Górski, Bartłomiej Masojć, Cezary Cybulski, Andrzej Kram, Romuald Maleszka, Tomasz Gromowski, Katarzyna Paszkowska-Szczur, Aniruddh Kashyap, Marcin R. Lener, Karolina Malińska, Emilia Rogoża, Dawid Murawa, Helena Rudnicka, Jakub Deptuła, Jan Lubiński
Cancer Res Treat. 2019;51(1):337-344.   Published online May 14, 2018
DOI: https://doi.org/10.4143/crt.2018.157
AbstractAbstract PDFPubReaderePub
Purpose
Germline mutations within melanoma susceptibility genes are present only in minority of melanoma patients and it is expected that additional genes will be discovered with next generation sequence technology and whole-exome sequencing (WES).
Materials and Methods
Herein we performed WES on a cohort of 96 unrelated Polish patients with melanoma diagnosed under the age of 40 years who all screened negative for the presence of CDKN2Avariants. A replication study using a set of 1,200 melanoma patient DNA samples and similarly large series of healthy controls was undertaken.
Results
We selected 21 potentially deleterious variants in 20 genes (VRK1, MYCT1, DNAH14, CASC3, MS4A12, PRC1, WWOX, CARD6, EXO5, CASC3, CASP8AP2, STK33, SAMD11, CNDP2, CPNE1, EFCAB6, CABLES1, LEKR1, NUDT17, and RRP15), which were identified by WES and confirmed by Sanger sequencing for an association study. Evaluation of the allele distribution among carriers and their relatives in available family trios revealed that these variants were unlikely to account for many familial cases of melanoma. Replication study revealed no statistically significant differences between cases and controls.
Conclusion
Although most of the changes seemed to be neutral we could not exclude an association between variants in VRK1, CREB3L3, EXO5, and STK33 with melanoma risk.

Citations

Citations to this article as recorded by  
  • Serine/Threonine Kinase (STK) 33 promotes the proliferation and metastasis of human esophageal squamous cell carcinoma via inflammation-related pathway
    Haifeng Jiang, Liping Li, Tao Ma, Ruixiao Wang, Xiaozhen Chen, Ke Xu, Chen Chen, Zijin Liu, Hongmei Wang, Lingyan Huang
    Pathology - Research and Practice.2024; 254: 155154.     CrossRef
  • Gene network-based and ensemble modeling-based selection of tumor-associated antigens with a predicted low risk of tissue damage for targeted immunotherapy
    Christopher Lischer, Martin Eberhardt, Cindy Flamann, Johannes Berges, Esther Güse, Anja Wessely, Adrian Weich, Jimmy Retzlaff, Jan Dörrie, Niels Schaft, Manuel Wiesinger, Johannes März, Beatrice Schuler-Thurner, Harald Knorr, Shailendra Gupta, Krishna Pa
    Journal for ImmunoTherapy of Cancer.2024; 12(5): e008104.     CrossRef
  • Investigating the mechanism of METTL16-dependent m6A modification regulating the SAMD11 protein signaling pathway to inhibit thyroid cancer phenotypes
    Yingming Liu, Gang Wu, Xingru Tao, Jiayu Dong, Tiefeng Shi, Chenlei Shi
    International Journal of Biological Macromolecules.2024; 280: 136176.     CrossRef
  • Identification and Validation of a m5C RNA Modification-Related Gene Signature for Predicting Prognosis and Immunotherapeutic Efficiency of Gastric Cancer
    Li Song, Shouguo Wang, Qiankun Li, Yao Lu, Rungong Yang, Xianqi Feng, İbrahim Hakkı Cigerci
    Journal of Oncology.2023; 2023: 1.     CrossRef
  • MYCT1 in cancer development: Gene structure, regulation, and biological implications for diagnosis and treatment
    Jianan Xu, Yuanyuan Sun, Weineng Fu, Shuang Fu
    Biomedicine & Pharmacotherapy.2023; 165: 115208.     CrossRef
  • Family-based whole-exome sequencing identifies rare variants potentially related to cutaneous melanoma predisposition in Brazilian melanoma-prone families
    Felipe Fidalgo, Giovana Tardin Torrezan, Bianca Costa Soares de Sá, Bruna Durães de Figueiredo Barros, Luciana Facure Moredo, Renan Valieris, Sandro J. de Souza, João Pereira Duprat, Ana Cristina Victorino Krepischi, Dirce Maria Carraro, Danillo G. August
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  • Unfolded protein response is involved in the metabolic and apoptotic regulation of oral squamous cell carcinoma
    B. Seo, D.E. Coates, J. Lewis, G.J. Seymour, A.M. Rich
    Pathology.2022; 54(7): 874.     CrossRef
  • Constitutional variants in POT1, TERF2IP, and ACD genes in patients with melanoma in the Polish population
    Karolina Malińska, Jakub Deptuła, Emilia Rogoża-Janiszewska, Bohdan Górski, Rodney Scott, Helena Rudnicka, Aniruddh Kashyap, Paweł Domagała, Jolanta Hybiak, Bartłomiej Masojć, Cezary Cybulski, Andrzej Kram, Magdalena Boer, Magdalena Kiedrowicz, Jan Lubińs
    European Journal of Cancer Prevention.2020; 29(6): 511.     CrossRef
  • A Systematic Literature Review of Whole Exome and Genome Sequencing Population Studies of Genetic Susceptibility to Cancer
    Melissa Rotunno, Rolando Barajas, Mindy Clyne, Elise Hoover, Naoko I. Simonds, Tram Kim Lam, Leah E. Mechanic, Alisa M. Goldstein, Elizabeth M. Gillanders
    Cancer Epidemiology, Biomarkers & Prevention.2020; 29(8): 1519.     CrossRef
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Serum Concentrations of Selenium and Copper in Patients Diagnosed with Pancreatic Cancer
Marcin R. Lener, Rodney J. Scott, Anna Wiechowska-Kozłowska, Pablo Serrano-Fernández, Piotr Baszuk, Katarzyna Jaworska-Bieniek, Grzegorz Sukiennicki, Wojciech Marciniak, Magdalena Muszyńska, Józef Kładny, Tomasz Gromowski, Katarzyna Kaczmarek, Anna Jakubowska, Jan Lubiński
Cancer Res Treat. 2016;48(3):1056-1064.   Published online December 28, 2015
DOI: https://doi.org/10.4143/crt.2015.282
AbstractAbstract PDFPubReaderePub
Purpose
Understanding of the etiology and pathogenesis of pancreatic cancer (PaCa) is still insufficient. This study evaluated the associations between concentrations of selenium (Se) and copper (Cu) in the serum of PaCa patients.
Materials and Methods
The study included 100 PaCa patients and 100 control subjects from the same geographical region in Poland. To determine the average concentration of Se, Cu, and ratio Cu:Se in the Polish population, assay for Se and Cu was performed in 480 healthy individuals. Serum levels of Se and Cu were measured using inductively coupled plasma mass spectrometry.
Results
In the control group, the average Se level was 76 µg/L and Cu 1,098 µg/L. The average Se level among PaCa patients was 60 µg/L and the mean Cu level was 1,432 µg/L. The threshold point at which any decrease in Se concentration was associated with PaCa was 67.45 µg/L. The threshold point of Cu level above which there was an increase in the prevalence of PaCa was 1,214.58 µg/L. In addition, a positive relationship was observed between increasing survival time and Se plasma level.
Conclusion
This retrospective study suggests that low levels of Se and high levels of Cu might influence development of PaCa and that higher levels of Se are associated with longer survival in patients with PaCa. The results suggest that determining the level of Se and Cu could be incorporated into a risk stratification scheme for the selection and surveillance control examination to complement existing screening and diagnostic procedures.

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