publication . Article . 2018

Two critical positions in zinc finger domains are heavily mutated in three human cancer types.

Daniel Munro; Mona Singh; Dario Ghersi;
Open Access
  • Published: 01 Jun 2018 Journal: PLOS Computational Biology, volume 14, page e1006290 (eissn: 1553-7358, Copyright policy)
  • Publisher: Public Library of Science (PLoS)
Abstract
A major goal of cancer genomics is to identify somatic mutations that play a role in tumor initiation or progression. Somatic mutations within transcription factors are of particular interest, as gene expression dysregulation is widespread in cancers. The substantial gene expression variation evident across tumors suggests that numerous regulatory factors are likely to be involved and that somatic mutations within them may not occur at high frequencies across patient cohorts, thereby complicating efforts to uncover which ones are cancer-relevant. Here we analyze somatic mutations within the largest family of human transcription factors, namely those that bind DN...
Subjects
free text keywords: Ecology, Modelling and Simulation, Computational Theory and Mathematics, Genetics, Ecology, Evolution, Behavior and Systematics, Molecular Biology, Cellular and Molecular Neuroscience, Biology (General), QH301-705.5, Research Article, Biology and Life Sciences, Missense Mutation, Somatic Mutation, Biochemistry, Proteins, Protein Domains, Zinc Finger Domains, DNA-binding proteins, Gene Expression, Substitution Mutation, DNA-binding protein, Point mutation, Biology, Cancer, medicine.disease, medicine, Mutation, medicine.disease_cause, Germline mutation, CYS2-HIS2 Zinc Fingers, Zinc finger, Gene
Funded by
NSF| Graduate Research Fellowship Program (GRFP)
Project
  • Funder: National Science Foundation (NSF)
  • Project Code: 1148900
  • Funding stream: Directorate for Education & Human Resources | Division of Graduate Education
,
NIH| Interaction-based computational methods for analyzing cancer genomes
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01CA208148-03
  • Funding stream: NATIONAL CANCER INSTITUTE
,
NIH| Predicting and analyzing protein interaction networks
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2R01GM076275-06
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
,
NSF| Discovery of Complex Recurring Protein Interaction Patterns within Interactomes: Algorithms, Applications and Software
Project
  • Funder: National Science Foundation (NSF)
  • Project Code: 0850063
  • Funding stream: Directorate for Biological Sciences | Division of Biological Infrastructure
47 references, page 1 of 4

1 Hudson TJ, Anderson W, Aretz A, Barker AD. International network of cancer genome projects. Nature. 2010;464(7291):993–8. doi: 10.1038/nature08987 20393554 [OpenAIRE] [PubMed]

2 Tomczak K, Czerwińska P, Wiznerowicz M. The Cancer Genome Atlas (TCGA): an immeasurable source of knowledge. Contemp Oncol. 2015;19(1A):A68–A77. [OpenAIRE]

3 Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, et al Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499:214–8. doi: 10.1038/nature12213 23770567 [OpenAIRE] [PubMed]

4 Stehr H, Jang SH, Duarte JM, Wierling C, Lehrach H, Lappe M, et al The structural impact of cancer-associated missense mutations in oncogenes and tumor suppressors. Mol Cancer. 2011;10:54 doi: 10.1186/1476-4598-10-54 21575214 [OpenAIRE] [PubMed]

5 Nishi H, Tyagi M, Teng S, Shoemaker B, Hashimoto K, Alexov E, et al Cancer missense mutations alter binding properties of proteins and their interaction networks. PLOS ONE. 2013;8(6):e66273 doi: 10.1371/journal.pone.0066273 23799087 [OpenAIRE] [PubMed]

6 Ghersi D, Singh M. Interaction-based discovery of functionally important genes in cancers. Nuc leic Acids Res. 2014;42(3):e18 doi: 10.1093/nar/gkt1305 24362839 [OpenAIRE] [PubMed]

7 Perou CM, Sorlie T, Eisen MB, Van De Rijn M, et al Molecular portraits of human breast tumours. Nature. 2000;406(6797):747 doi: 10.1038/35021093 10963602 [OpenAIRE] [PubMed]

8 Hollstein M, Sidransky D, Vogelstein B, Harris C. p53 mutations in human cancers. Science. 1991;253(5015):49–53. doi: 10.1126/science.1905840 1905840 [OpenAIRE] [PubMed]

9 Shain AH, Pollack JR. The spectrum of SWI/SNF mutations, ubiquitous in human cancers. PLOS ONE. 2013;8(1):e55119 doi: 10.1371/journal.pone.0055119 23355908 [OpenAIRE] [PubMed]

10 The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumors. Nature. 2012;490(7418):61 doi: 10.1038/nature11412 23000897 [OpenAIRE] [PubMed]

11 Vaquerizas J, Kummerfeld S, Teichmann S, Luscombe N. A census of human transcription factors: function, expression and evolution. Nature Review Genetics. 2009;10 doi: 10.1038/nrg2538 [OpenAIRE]

12 Urrutia R. KRAB-containing zinc-finger repressor proteins. Genome Biology. 2003;4(10):1 doi: 10.1186/gb-2003-4-10-231

13 Lupo A, Cesaro E, Montano G, Zurlo D, Izzo P, Costanzo P. KRAB-Zinc finger proteins: A repressor family displaying multiple biological functions. Current Genomics. 2013;14(4):268–278. doi: 10.2174/13892029113149990002 24294107 [OpenAIRE] [PubMed]

14 Liu H, Chang LH, Sun Y, Lu X, Stubbs L. Deep vertebrate roots for mammalian zinc finger transcription factor subfamilies. Genome Biol Evol. 2014;6(3):510–525. doi: 10.1093/gbe/evu030 24534434 [OpenAIRE] [PubMed]

15 Wolf D, Goff S. Embryonic stem cells use ZFP809 to silence retroviral DNAs. Nature. 2009;458:1201–1204. doi: 10.1038/nature07844 19270682 [OpenAIRE] [PubMed]

47 references, page 1 of 4
Abstract
A major goal of cancer genomics is to identify somatic mutations that play a role in tumor initiation or progression. Somatic mutations within transcription factors are of particular interest, as gene expression dysregulation is widespread in cancers. The substantial gene expression variation evident across tumors suggests that numerous regulatory factors are likely to be involved and that somatic mutations within them may not occur at high frequencies across patient cohorts, thereby complicating efforts to uncover which ones are cancer-relevant. Here we analyze somatic mutations within the largest family of human transcription factors, namely those that bind DN...
Subjects
free text keywords: Ecology, Modelling and Simulation, Computational Theory and Mathematics, Genetics, Ecology, Evolution, Behavior and Systematics, Molecular Biology, Cellular and Molecular Neuroscience, Biology (General), QH301-705.5, Research Article, Biology and Life Sciences, Missense Mutation, Somatic Mutation, Biochemistry, Proteins, Protein Domains, Zinc Finger Domains, DNA-binding proteins, Gene Expression, Substitution Mutation, DNA-binding protein, Point mutation, Biology, Cancer, medicine.disease, medicine, Mutation, medicine.disease_cause, Germline mutation, CYS2-HIS2 Zinc Fingers, Zinc finger, Gene
Funded by
NSF| Graduate Research Fellowship Program (GRFP)
Project
  • Funder: National Science Foundation (NSF)
  • Project Code: 1148900
  • Funding stream: Directorate for Education & Human Resources | Division of Graduate Education
,
NIH| Interaction-based computational methods for analyzing cancer genomes
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01CA208148-03
  • Funding stream: NATIONAL CANCER INSTITUTE
,
NIH| Predicting and analyzing protein interaction networks
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2R01GM076275-06
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
,
NSF| Discovery of Complex Recurring Protein Interaction Patterns within Interactomes: Algorithms, Applications and Software
Project
  • Funder: National Science Foundation (NSF)
  • Project Code: 0850063
  • Funding stream: Directorate for Biological Sciences | Division of Biological Infrastructure
47 references, page 1 of 4

1 Hudson TJ, Anderson W, Aretz A, Barker AD. International network of cancer genome projects. Nature. 2010;464(7291):993–8. doi: 10.1038/nature08987 20393554 [OpenAIRE] [PubMed]

2 Tomczak K, Czerwińska P, Wiznerowicz M. The Cancer Genome Atlas (TCGA): an immeasurable source of knowledge. Contemp Oncol. 2015;19(1A):A68–A77. [OpenAIRE]

3 Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, et al Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499:214–8. doi: 10.1038/nature12213 23770567 [OpenAIRE] [PubMed]

4 Stehr H, Jang SH, Duarte JM, Wierling C, Lehrach H, Lappe M, et al The structural impact of cancer-associated missense mutations in oncogenes and tumor suppressors. Mol Cancer. 2011;10:54 doi: 10.1186/1476-4598-10-54 21575214 [OpenAIRE] [PubMed]

5 Nishi H, Tyagi M, Teng S, Shoemaker B, Hashimoto K, Alexov E, et al Cancer missense mutations alter binding properties of proteins and their interaction networks. PLOS ONE. 2013;8(6):e66273 doi: 10.1371/journal.pone.0066273 23799087 [OpenAIRE] [PubMed]

6 Ghersi D, Singh M. Interaction-based discovery of functionally important genes in cancers. Nuc leic Acids Res. 2014;42(3):e18 doi: 10.1093/nar/gkt1305 24362839 [OpenAIRE] [PubMed]

7 Perou CM, Sorlie T, Eisen MB, Van De Rijn M, et al Molecular portraits of human breast tumours. Nature. 2000;406(6797):747 doi: 10.1038/35021093 10963602 [OpenAIRE] [PubMed]

8 Hollstein M, Sidransky D, Vogelstein B, Harris C. p53 mutations in human cancers. Science. 1991;253(5015):49–53. doi: 10.1126/science.1905840 1905840 [OpenAIRE] [PubMed]

9 Shain AH, Pollack JR. The spectrum of SWI/SNF mutations, ubiquitous in human cancers. PLOS ONE. 2013;8(1):e55119 doi: 10.1371/journal.pone.0055119 23355908 [OpenAIRE] [PubMed]

10 The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumors. Nature. 2012;490(7418):61 doi: 10.1038/nature11412 23000897 [OpenAIRE] [PubMed]

11 Vaquerizas J, Kummerfeld S, Teichmann S, Luscombe N. A census of human transcription factors: function, expression and evolution. Nature Review Genetics. 2009;10 doi: 10.1038/nrg2538 [OpenAIRE]

12 Urrutia R. KRAB-containing zinc-finger repressor proteins. Genome Biology. 2003;4(10):1 doi: 10.1186/gb-2003-4-10-231

13 Lupo A, Cesaro E, Montano G, Zurlo D, Izzo P, Costanzo P. KRAB-Zinc finger proteins: A repressor family displaying multiple biological functions. Current Genomics. 2013;14(4):268–278. doi: 10.2174/13892029113149990002 24294107 [OpenAIRE] [PubMed]

14 Liu H, Chang LH, Sun Y, Lu X, Stubbs L. Deep vertebrate roots for mammalian zinc finger transcription factor subfamilies. Genome Biol Evol. 2014;6(3):510–525. doi: 10.1093/gbe/evu030 24534434 [OpenAIRE] [PubMed]

15 Wolf D, Goff S. Embryonic stem cells use ZFP809 to silence retroviral DNAs. Nature. 2009;458:1201–1204. doi: 10.1038/nature07844 19270682 [OpenAIRE] [PubMed]

47 references, page 1 of 4
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