Cancerouspdomains: comprehensive analysis of cancer type-specific recurrent somatic mutations in proteins and domains

BackgroundDiscriminating driver mutations from the ones that play no role in cancer is a severe bottleneck in elucidating molecular mechanisms underlying cancer development. Since protein domains are representatives of functional regions within proteins, mutations on them may disturb the protein functionality. Therefore, studying mutations at domain level may point researchers to more accurate assessment of the functional impact of the mutations.ResultsThis article presents a comprehensive study to map mutations from 29 cancer types to both sequence- and structure-based domains. Statistical analysis was performed to identify candidate domains in which mutations occur with high statistical significance. For each cancer type, the corresponding type-specific domains were distinguished among all candidate domains. Subsequently, cancer type-specific domains facilitated the identification of specific proteins for each cancer type. Besides, performing interactome analysis on specific proteins of each cancer type showed high levels of interconnectivity among them, which implies their functional relationship. To evaluate the role of mitochondrial genes, stem cell-specific genes and DNA repair genes in cancer development, their mutation frequency was determined via further analysis.ConclusionsThis study has provided researchers with a publicly available data repository for studying both CATH and Pfam domain regions on protein-coding genes. Moreover, the associations between different groups of genes/domains and various cancer types have been clarified. The work is available at http://www.cancerouspdomains.ir.

[1]  Zev A. Binder,et al.  The Genetic Landscape of the Childhood Cancer Medulloblastoma , 2011, Science.

[2]  P. Jeggo,et al.  DNA repair, genome stability and cancer: a historical perspective , 2015, Nature Reviews Cancer.

[3]  M. Meyers,et al.  Keratin: Structure, mechanical properties, occurrence in biological organisms, and efforts at bioinspiration , 2016 .

[4]  Christoph Lahtz,et al.  Epigenetic changes of DNA repair genes in cancer. , 2011, Journal of molecular cell biology.

[5]  L. Migliore,et al.  Mutation Research / Fundamental and Molecular Mechanisms of Mutagenesis , 2014 .

[6]  G J Williams,et al.  The Protein Data Bank: a computer-based archival file for macromolecular structures. , 1978, Archives of biochemistry and biophysics.

[7]  Eric R. Ziegel,et al.  Probability and Statistics for Engineering and the Sciences , 2004, Technometrics.

[8]  A. Børresen-Dale,et al.  TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes , 2007, Oncogene.

[9]  Terrence S. Furey,et al.  The UCSC Table Browser data retrieval tool , 2004, Nucleic Acids Res..

[10]  David A. Lee,et al.  CATH: comprehensive structural and functional annotations for genome sequences , 2014, Nucleic Acids Res..

[11]  Joshua M. Stuart,et al.  The Cancer Genome Atlas Pan-Cancer analysis project , 2013, Nature Genetics.

[12]  I. Weissman,et al.  Stem cells, cancer, and cancer stem cells , 2001, Nature.

[13]  Jason Kaplan,et al.  Genomic landscape of DNA repair genes in cancer , 2016, Oncotarget.

[14]  Magali Olivier,et al.  TP53 mutations in human cancers: origins, consequences, and clinical use. , 2010, Cold Spring Harbor perspectives in biology.

[15]  M. Haigis,et al.  Mitochondria and Cancer , 2016, Cell.

[16]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[17]  R. Seruca,et al.  Microsatellite instability, mitochondrial DNA large deletions, and mitochondrial DNA mutations in gastric carcinoma , 2001, Genes, chromosomes & cancer.

[18]  E. Birney,et al.  Pfam: the protein families database , 2013, Nucleic Acids Res..

[19]  Richard D. Wood,et al.  Human DNA Repair Genes , 2001, Science.

[20]  D. Hanahan,et al.  Hallmarks of Cancer: The Next Generation , 2011, Cell.

[21]  J. Lubiński,et al.  CHEK2 is a multiorgan cancer susceptibility gene. , 2004, American journal of human genetics.

[22]  Katsuya Yamashita,et al.  Mitochondrial D-loop mutations as clonal markers in multicentric hepatocellular carcinoma and plasma. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[23]  Eric S. Lander,et al.  The genomic complexity of primary human prostate cancer , 2010, Nature.

[24]  R. Wood,et al.  DNA polymerases and cancer , 2011, Nature Reviews Cancer.

[25]  Thomas A. Peterson,et al.  Domain landscapes of somatic mutations in cancer , 2012, BMC Genomics.

[26]  Fan Yang,et al.  Protein Domain-Level Landscape of Cancer-Type-Specific Somatic Mutations , 2015, PLoS Comput. Biol..

[27]  Yu Liang,et al.  Gene expression in stem cells. , 2009, Critical reviews in eukaryotic gene expression.

[28]  Rebecca L. Siegel Mph,et al.  Cancer statistics, 2016 , 2016 .

[29]  Nobuyuki Itoh,et al.  Fibroblast growth factors , 2001, Genome Biology.

[30]  E. Friedberg,et al.  DNA Repair and Mutagenesis , 2006 .

[31]  Yali Dou,et al.  Hijacked in cancer: the KMT2 (MLL) family of methyltransferases , 2015, Nature Reviews Cancer.

[32]  M. López-Lázaro,et al.  The migration ability of stem cells can explain the existence of cancer of unknown primary site. Rethinking metastasis , 2015, Oncoscience.

[33]  Douglas C. Wallace,et al.  Accumulation of mitochondrial DNA deletions in the malignant prostate of patients of different ages , 2001, Experimental Gerontology.

[34]  Deanna M. Church,et al.  Genome Reference Consortium , 2013 .

[35]  C. Mathers,et al.  GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer , 2013 .

[36]  A. Cheung,et al.  High incidence of somatic mitochondrial DNA mutations in human ovarian carcinomas. , 2001, Cancer research.

[37]  David C. Jones,et al.  CATH--a hierarchic classification of protein domain structures. , 1997, Structure.

[38]  Gary S. Stein,et al.  Human stem cell technology and biology : a research guide and laboratory manual , 2010 .

[39]  Javier De Las Rivas,et al.  Protein–Protein Interactions Essentials: Key Concepts to Building and Analyzing Interactome Networks , 2010, PLoS Comput. Biol..

[40]  L. Hays,et al.  Mitochondrial DNA copy number changes in human gliomas. , 1996, Cancer letters.

[41]  Jae-Hong Ko,et al.  Non-Silent Story on Synonymous Sites in Voltage-Gated Ion Channel Genes , 2012, PloS one.

[42]  G. Cavet,et al.  Inferring the functional effects of mutation through clusters of mutations in homologous proteins , 2010, Human mutation.

[43]  E Gabrielson,et al.  Detection of mitochondrial DNA mutations in primary breast cancer and fine-needle aspirates. , 2001, Cancer research.

[44]  Bonnie Berger,et al.  A gene expression profile of stem cell pluripotentiality and differentiation is conserved across diverse solid and hematopoietic cancers , 2012, Genome Biology.

[45]  G. Parmigiani,et al.  The Consensus Coding Sequences of Human Breast and Colorectal Cancers , 2006, Science.

[46]  L. Goddard Information Theory , 1962, Nature.

[47]  Mingming Jia,et al.  COSMIC: exploring the world's knowledge of somatic mutations in human cancer , 2014, Nucleic Acids Res..

[48]  Maria Jesus Martin,et al.  SIFTS: Structure Integration with Function, Taxonomy and Sequences resource , 2012, Nucleic Acids Res..

[49]  Andy P. Field,et al.  Discovering Statistics Using SPSS , 2000 .

[50]  K. Tomczak,et al.  The Cancer Genome Atlas (TCGA): an immeasurable source of knowledge , 2015, Contemporary oncology.

[51]  A. Sparks,et al.  The Genomic Landscapes of Human Breast and Colorectal Cancers , 2007, Science.

[52]  P. Soares,et al.  Mitochondrial DNA somatic mutations (point mutations and large deletions) and mitochondrial DNA variants in human thyroid pathology: a study with emphasis on Hürthle cell tumors. , 2002, The American journal of pathology.

[53]  Davide Heller,et al.  STRING v10: protein–protein interaction networks, integrated over the tree of life , 2014, Nucleic Acids Res..

[54]  Ping Sun,et al.  CHEK2 mutations and the risk of papillary thyroid cancer , 2015, International journal of cancer.

[55]  N. Dubrawsky Cancer statistics , 1989, CA: a cancer journal for clinicians.

[56]  Elspeth A. Bruford,et al.  Genenames.org: the HGNC resources in 2015 , 2014, Nucleic Acids Res..

[57]  Tomas Lindahl,et al.  Human DNA repair genes, 2005. , 2005, Mutation research.

[58]  M. López-Lázaro,et al.  The stem cell division theory of cancer. , 2018, Critical reviews in oncology/hematology.

[59]  Pablo Cingolani,et al.  © 2012 Landes Bioscience. Do not distribute. , 2022 .

[60]  Anthony Jf Griffiths,et al.  Modern genetic analysis : integrating genes and genomes , 2002 .

[61]  A. Jemal,et al.  Cancer statistics, 2016 , 2016, CA: a cancer journal for clinicians.

[62]  Jelle J. Goeman,et al.  Multiple hypothesis testing in genomics , 2014, Statistics in medicine.

[63]  D. Wallace,et al.  Novel mitochondrial DNA deletion found in a renal cell carcinoma , 1996, Genes, chromosomes & cancer.

[64]  L. Holm,et al.  The Pfam protein families database , 2005, Nucleic Acids Res..