Landscape of genomic alterations in cervical carcinomas (original) (raw)

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Data deposits

Sequence data used for this analysis are available in dbGaP under accession phs000600.

References

  1. Jemal, A. et al. Global cancer statistics. CA Cancer J. Clin. 61, 69–90 (2011)
    PubMed Google Scholar
  2. International Agency for Research on Cancer. A review of human carcinogen: biological agents. in IARC Monographs on the Evaluation of Carcinogenic Risks to Humans Vol. 100B (International Agency for Research on Cancer, 2012)
  3. zur Hausen, H. Papillomaviruses in the causation of human cancers — a brief historical account. Virology 384, 260–265 (2009)
    CAS PubMed Google Scholar
  4. Crook, T. et al. Clonal p53 mutation in primary cervical cancer: association with human-papillomavirus-negative tumours. Lancet 339, 1070–1073 (1992)
    CAS PubMed Google Scholar
  5. McIntyre, J. B. et al. PIK3CA mutational status and overall survival in patients with cervical cancer treated with radical chemoradiotherapy. Gynecol. Oncol. 128, 409–414 (2013)
    CAS PubMed Google Scholar
  6. Kang, S. et al. Inverse correlation between RASSF1A hypermethylation, KRAS and BRAF mutations in cervical adenocarcinoma. Gynecol. Oncol. 105, 662–666 (2007)
    CAS PubMed Google Scholar
  7. Wingo, S. N. et al. Somatic LKB1 mutations promote cervical cancer progression. PLoS ONE 4, e5137 (2009)
    ADS PubMed PubMed Central Google Scholar
  8. Narayan, G. & Murty, V. V. Integrative genomic approaches in cervical cancer: implications for molecular pathogenesis. Future Oncol. 6, 1643–1652 (2010)
    CAS PubMed Google Scholar
  9. Vazquez-Mena, O. et al. Amplified genes may be overexpressed, unchanged, or downregulated in cervical cancer cell lines. PLoS ONE 7, e32667 (2012)
    ADS CAS PubMed PubMed Central Google Scholar
  10. Arteaga, C. L. & Baselga, J. Impact of genomics on personalized cancer medicine. Clin. Cancer Res. 18, 612–618 (2012)
    CAS PubMed Google Scholar
  11. Cibulskis, K. et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nature Biotechnol. 31, 213–219 (2013)
    CAS Google Scholar
  12. Lawrence, M. S. et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499, 214–218 (2013)
    ADS CAS PubMed PubMed Central Google Scholar
  13. Lohr, J. G. et al. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc. Natl Acad. Sci. USA 109, 3879–3884 (2012)
    ADS CAS PubMed PubMed Central Google Scholar
  14. Greulich, H. et al. Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2. Proc. Natl Acad. Sci. USA 109, 14476–14481 (2012)
    ADS CAS PubMed PubMed Central Google Scholar
  15. Bose, R. et al. Activating HER2 mutations in HER2 gene amplification negative breast cancer. Cancer Discov. 3, 224–237 (2012)
    PubMed PubMed Central Google Scholar
  16. Arvind, R. et al. A mutation in the common docking domain of ERK2 in a human cancer cell line, which was associated with its constitutive phosphorylation. Int. J. Oncol. 27, 1499–1504 (2005)
    CAS PubMed Google Scholar
  17. De Luca, A., Maiello, M. R., D’Alessio, A., Pergameno, M. & Normanno, N. The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opin. Ther. Targets 16 (Suppl. 2). S17–S27 (2012)
    CAS PubMed Google Scholar
  18. Le Gallo, M. et al. Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes. Nature Genet. 44, 1310–1315 (2012)
    CAS PubMed Google Scholar
  19. Agrawal, N. et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science 333, 1154–1157 (2011)
    ADS CAS PubMed PubMed Central Google Scholar
  20. Chen, J., Ghazawi, F. M. & Li, Q. Interplay of bromodomain and histone acetylation in the regulation of p300-dependent genes. Epigenetics 5, 509–515 (2010)
    CAS PubMed PubMed Central Google Scholar
  21. Smith, T. F., Gaitatzes, C., Saxena, K. & Neer, E. J. The WD repeat: a common architecture for diverse functions. Trends Biochem. Sci. 24, 181–185 (1999)
    CAS PubMed Google Scholar
  22. Tong, K. I. et al. Keap1 recruits Neh2 through binding to ETGE and DLG motifs: characterization of the two-site molecular recognition model. Mol. Cell. Biol. 26, 2887–2900 (2006)
    CAS PubMed PubMed Central Google Scholar
  23. Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature 489, 519–525 (2012)
  24. Pamer, E. & Cresswell, P. Mechanisms of MHC class I-restricted antigen processing. Annu. Rev. Immunol. 16, 323–358 (1998)
    CAS PubMed Google Scholar
  25. Neve, R. M., Ylstra, B., Chang, C. H., Albertson, D. G. & Benz, C. C. ErbB2 activation of ESX gene expression. Oncogene 21, 3934–3938 (2002)
    CAS PubMed Google Scholar
  26. Wentzensen, N., Vinokurova, S. & von Knebel Doeberitz, M. Systematic review of genomic integration sites of human papillomavirus genomes in epithelial dysplasia and invasive cancer of the female lower genital tract. Cancer Res. 64, 3878–3884 (2004)
    CAS PubMed Google Scholar
  27. Kraus, I. et al. The majority of viral-cellular fusion transcripts in cervical carcinomas cotranscribe cellular sequences of known or predicted genes. Cancer Res. 68, 2514–2522 (2008)
    CAS PubMed Google Scholar
  28. Schmitz, M., Driesch, C., Jansen, L., Runnebaum, I. B. & Durst, M. Non-random integration of the HPV genome in cervical cancer. PLoS ONE 7, e39632 (2012)
    ADS CAS PubMed PubMed Central Google Scholar
  29. Tang, K. W., Alaei-Mahabadi, B., Samuelsson, T., Lindh, M. & Larsson, E. The landscape of viral expression and host gene fusion and adaptation in human cancer. Nature Commun. 4, 2513 (2013)
    ADS Google Scholar
  30. Peter, M. et al. Frequent genomic structural alterations at HPV insertion sites in cervical carcinoma. J. Pathol. 221, 320–330 (2010)
    CAS PubMed Google Scholar
  31. Gnirke, A. et al. Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing. Nature Biotechnol. 27, 182–189 (2009)
    CAS Google Scholar
  32. Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25, 1754–1760 (2009)
    Article CAS PubMed PubMed Central Google Scholar
  33. Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009)
    PubMed PubMed Central Google Scholar
  34. Stransky, N. et al. The mutational landscape of head and neck squamous cell carcinoma. Science 333, 1157–1160 (2011)
    ADS CAS PubMed PubMed Central Google Scholar
  35. Banerji, S. et al. Sequence analysis of mutations and translocations across breast cancer subtypes. Nature 486, 405–409 (2012)
    ADS CAS PubMed PubMed Central Google Scholar
  36. Lee, R. S. et al. A remarkably simple genome underlies highly malignant pediatric rhabdoid cancers. J. Clin. Invest. 122, 2983–2988 (2012)
    CAS PubMed PubMed Central Google Scholar
  37. Berger, M. F. et al. The genomic complexity of primary human prostate cancer. Nature 470, 214–220 (2011)
    ADS CAS PubMed PubMed Central Google Scholar
  38. Chapman, M. A. et al. Initial genome sequencing and analysis of multiple myeloma. Nature 471, 467–472 (2011)
    ADS CAS PubMed PubMed Central Google Scholar
  39. Cibulskis, K. et al. ContEst: estimating cross-contamination of human samples in next-generation sequencing data. Bioinformatics 27, 2601–2602 (2011)
    CAS PubMed PubMed Central Google Scholar
  40. Forbes, S. A. et al. COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res. 39, D945–D950 (2011)
    CAS PubMed Google Scholar
  41. DePristo, M. A. et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nature Genet. 43, 491–498 (2011)
    CAS PubMed Google Scholar
  42. McKenna, A. et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297–1303 (2010)
    CAS PubMed PubMed Central Google Scholar
  43. Carter, S. L. et al. Absolute quantification of somatic DNA alterations in human cancer. Nature Biotechnol. 30, 413–421 (2012)
    CAS Google Scholar
  44. Erlich, H. HLA DNA typing: past, present, and future. Tissue Antigens 80, 1–11 (2012)
    CAS PubMed Google Scholar
  45. Ward, J. H., Jr Hierarchical grouping to optimize an objective function. J. Am. Stat. Assoc. 58, 236–244 (1963)
    MathSciNet Google Scholar
  46. Trapnell, C. et al. Differential analysis of gene regulation at transcript resolution with RNA-seq. Nature Biotechnol. 31, 46–63 (2012)
    Google Scholar
  47. Bass, A. J. et al. Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion. Nature Genet. 43, 964–968 (2011)
    CAS PubMed Google Scholar
  48. Pleasance, E. D. et al. A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 463, 191–196 (2010)
    ADS CAS PubMed Google Scholar
  49. Wilkerson, M. D. & Hayes, D. N. ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking. Bioinformatics 26, 1572–1573 (2010)
    CAS PubMed PubMed Central Google Scholar
  50. Cañadas, M. P. et al. Comparison of the f-HPV typing and Hybrid Capture II assays for detection of high-risk HPV genotypes in cervical samples. J. Virol. Methods 183, 14–18 (2012)
    PubMed Google Scholar
  51. Walline, H. M. et al. High-risk human papillomavirus detection in oropharyngeal, nasopharyngeal, and, oral cavity cancers: comparison of multiple methods. JAMA Otolaryngol. Head Neck Surg. http://dx.doi.org/10.1001/jamaoto.2013.5460. (31 October 2013)
  52. Yang, H. et al. Sensitive detection of human papillomavirus in cervical, head/neck, and schistosomiasis-associated bladder malignancies. Proc. Natl Acad. Sci. USA 102, 7683–7688 (2005)
    ADS CAS PubMed PubMed Central Google Scholar
  53. Kostic, A. D. et al. PathSeq: software to identify or discover microbes by deep sequencing of human tissue. Nature Biotechnol. 29, 393–396 (2011)
    CAS Google Scholar
  54. Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005)
    ADS CAS PubMed PubMed Central Google Scholar
  55. Harris, R. S. & Liddament, M. T. Retroviral restriction by APOBEC proteins. Nature Rev. Immunol. 4, 868–877 (2004)
    CAS Google Scholar
  56. Roberts, S. A. et al. An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nature Genet. 45, 970–976 (2013)
    CAS PubMed Google Scholar

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Acknowledgements

This work was conducted as part of the Slim Initiative for Genomic Medicine in the Americas, a project funded by the Carlos Slim Health Institute in Mexico. This work was also partially supported by the Rebecca Ridley Kry Fellowship of the Damon Runyon Cancer Research Foundation (A.I.O.); MMRF Research Fellow Award (A.I.O.); Helse Vest, Research Council of Norway, Norwegian Cancer Society and Harald Andersens legat (H.B.S.); CONACyT grant SALUD-2008-C01-87625 and UANL PAICyT grant CS1038-1 (H.A.B.-S.); and CONACyT grant 161619 (J.M.-Z.). We also thank B. Edvardsen, K. Dahl-Michelsen, Å. Mokleiv, K. Madisso, T. Njølstad and E. Valen for technical and programmatic assistance; the staff of the Broad Institute Genomics Platform for their assistance in processing samples and generating the sequencing data used in the analyses; the Instituto Mexicano del Seguro Social (IMSS) for their Support; and L. Gaffney of Broad Institute Communications for figure layout and design.

Author information

Author notes

  1. Akinyemi I. Ojesina, Lee Lichtenstein, Helga B. Salvesen and Matthew Meyerson: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 02215, Massachusetts, USA
    Akinyemi I. Ojesina, Chandra Sekhar Pedamallu, Trevor J. Pugh, Alexi A. Wright, Fujiko Duke, Bethany Kaplan, Rui Wang, Heidi Greulich & Matthew Meyerson
  2. The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, 02142, Massachusetts, USA
    Akinyemi I. Ojesina, Lee Lichtenstein, Samuel S. Freeman, Chandra Sekhar Pedamallu, Trevor J. Pugh, Andrew D. Cherniack, Lauren Ambrogio, Kristian Cibulskis, Mara W. Rosenberg, Bethany Kaplan, Elizabeth Nickerson, Michael S. Lawrence, Chip Stewart, Scott L. Carter, Aaron McKenna, Maria L. Cortes, Heidi Greulich, Stacey B. Gabriel, Gad Getz & Matthew Meyerson
  3. Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico,
    Ivan Imaz-Rosshandler, Sandra Romero-Cordoba, Karla Vazquez-Santillan, Alberto Salido Guadarrama, Magali Espinosa-Castilla, Nayeli Belem Gabiño, Alfredo Hidalgo-Miranda, Claudia Rangel Escareno & Jorge Melendez-Zajgla
  4. Department of Pathology, Haukeland University Hospital, N5021 Bergen, Norway,
    Bjørn Bertelsen, Lars A. Akslen & Olav K. Vintermyr
  5. Tecnológico de Monterrey, Monterrey 64849, Mexico,
    Victor Treviño
  6. Department of Medicine, Brigham and Women’s Hospital, Boston, 02115, Massachusetts, USA
    Alexi A. Wright & Heidi Greulich
  7. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
    Rui Wang
  8. Cancer Biology Program, Program in the Biomedical Sciences, Rackham Graduate School, University of Michigan, Ann Arbor, 48109, Michigan, USA
    Heather M. Walline
  9. Facultad de Medicina y Hospital Universitario ‘Dr. José Eluterio González’ de la Universidad Autónoma de Nuevo León, Monterrey, Nuevo León 64460, México,
    Iram P. Rodriguez-Sanchez, Gabriela Sofia Gómez-Macías, Lezmes D. Valdez-Chapa, María Lourdes Garza-Rodríguez & Hugo A. Barrera-Saldaña
  10. Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway,
    Kathrine Woie, Line Bjorge, Elisabeth Wik, Mari K. Halle, Erling A. Hoivik, Camilla Krakstad & Helga B. Salvesen
  11. Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, N5020 Bergen, Norway,
    Line Bjorge, Elisabeth Wik, Mari K. Halle, Erling A. Hoivik, Camilla Krakstad & Helga B. Salvesen
  12. Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico,
    German Maytorena, Jorge Vazquez, Carlos Rodea & Adrian Cravioto
  13. Department of Pathology, Brigham and Women’s Hospital, Boston, 02115, Massachusetts, USA
    Christopher P. Crum & Matthew Meyerson
  14. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, 02215, Massachusetts, USA
    Donna S. Neuberg
  15. Claremont Graduate University, Claremont, 91711, California, USA
    Claudia Rangel Escareno
  16. Department of Clinical Medicine, Centre for Cancer Biomarkers, University of Bergen, N5020 Bergen, Norway,
    Lars A. Akslen & Olav K. Vintermyr
  17. Head and Neck Oncology Program and Department of Otolaryngology, University of Michigan Comprehensive Cancer Center, Ann Arbor, 38109, Michigan, USA
    Thomas E. Carey
  18. Massachusetts General Hospital Cancer Center and Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, Massachusetts, USA
    Gad Getz

Authors

  1. Akinyemi I. Ojesina
  2. Lee Lichtenstein
  3. Samuel S. Freeman
  4. Chandra Sekhar Pedamallu
  5. Ivan Imaz-Rosshandler
  6. Trevor J. Pugh
  7. Andrew D. Cherniack
  8. Lauren Ambrogio
  9. Kristian Cibulskis
  10. Bjørn Bertelsen
  11. Sandra Romero-Cordoba
  12. Victor Treviño
  13. Karla Vazquez-Santillan
  14. Alberto Salido Guadarrama
  15. Alexi A. Wright
  16. Mara W. Rosenberg
  17. Fujiko Duke
  18. Bethany Kaplan
  19. Rui Wang
  20. Elizabeth Nickerson
  21. Heather M. Walline
  22. Michael S. Lawrence
  23. Chip Stewart
  24. Scott L. Carter
  25. Aaron McKenna
  26. Iram P. Rodriguez-Sanchez
  27. Magali Espinosa-Castilla
  28. Kathrine Woie
  29. Line Bjorge
  30. Elisabeth Wik
  31. Mari K. Halle
  32. Erling A. Hoivik
  33. Camilla Krakstad
  34. Nayeli Belem Gabiño
  35. Gabriela Sofia Gómez-Macías
  36. Lezmes D. Valdez-Chapa
  37. María Lourdes Garza-Rodríguez
  38. German Maytorena
  39. Jorge Vazquez
  40. Carlos Rodea
  41. Adrian Cravioto
  42. Maria L. Cortes
  43. Heidi Greulich
  44. Christopher P. Crum
  45. Donna S. Neuberg
  46. Alfredo Hidalgo-Miranda
  47. Claudia Rangel Escareno
  48. Lars A. Akslen
  49. Thomas E. Carey
  50. Olav K. Vintermyr
  51. Stacey B. Gabriel
  52. Hugo A. Barrera-Saldaña
  53. Jorge Melendez-Zajgla
  54. Gad Getz
  55. Helga B. Salvesen
  56. Matthew Meyerson

Contributions

A.I.O., L.L., S.S.F., C.S.P., H.B.S. and M.M. wrote the manuscript with help from co-authors. A.I.O., L.L., K.C., C.S. and G.G. performed whole exome and genome sequencing data analysis. A.I.O., I.I., V.T., K.V.-S., A.S.G., S.R.-C., C.R.E., S.S.F. and C.S.P. performed RNA sequencing data analysis. A.I.O., S.S.F., C.S.P. and T.J.P. performed HPV integration analyses. A.I.O. and A.D.C. performed copy-number analyses. A.I.O., F.D., B.K., R.W. and H.G. performed functional experiments on MAPK1. B.B., N.B.G., G.S.G.-M. and C.P.C. facilitated and performed pathology review. O.K.V., H.M.W. and T.E.C. performed HPV status determination. L.A., E.N. and M.L.C. facilitated project management. L.L., I.I.-R., V.T., K.V.-S., A.S.G., S.R.-C., I.P.R.-S. and C.R.E. performed sequencing data validation. M.E.-C., M.K.H., E.W., E.A.H., C.K. and M.L.G.-R. performed specimen processing, biobanking and data management. K.W., L.B., L.D.V.-C., G.M., J.V., C.R., A.C. and H.B.S. collected patient materials and clinical information. A.I.O., L.L. and D.S.N. performed biostatistical and epidemiological analyses. A.I.O., L.L., S.S.F., C.S.P., I.I.-R., T.J.P., A.D.C., V.T., A.A.W., M.W.R., F.D., M.S.L., C.S., S.L.C., A.M., H.B.S. and M.M. contributed text, figures (including Supplementary Information) and analytical tools. A.H.-M., C.R.E., L.A.A., S.B.G., H.A.B.-S., J.M.-Z., G.G., H.B.S. and M.M. provided leadership for the project. All authors contributed to the final manuscript. Lead authors A.I.O. and L.L. and senior authors M.M. and H.B.S. contributed equally to this work.

Corresponding authors

Correspondence toHelga B. Salvesen or Matthew Meyerson.

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Competing interests

M.M. holds equity in, and consults for, Foundation Medicine.

Supplementary information

Supplementary Information

This file contains Supplementary Notes 1-15 with additional references (see Contents for more details), Supplementary Figures 1-30 and Supplementary Tables 1-11, 13 and 15-21 (see separate files for tables 12 and 14). (PDF 5727 kb)

Supplementary Table 12

This zipped file contains the correlation between RNASeq-derived gene expression and WES-derived copy number across 16898 genes, as well as the full complement of the raw values for these two parameters for 79 tumors with RNASeq data. (ZIP 30025 kb)

Supplementary Table 14

This file contains details of HPV typing and viral integration analyses. (XLSX 56 kb)

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Ojesina, A., Lichtenstein, L., Freeman, S. et al. Landscape of genomic alterations in cervical carcinomas.Nature 506, 371–375 (2014). https://doi.org/10.1038/nature12881

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