Abstract
High-throughput cancer genomics and bioinformatics are revolutionizing our ability to profile tumor samples. With next-generation sequencing (NGS) and high-performance computing (HPC) platforms, we have developed the infrastructures to determine and characterize tumor genomes and transcriptomes within days. Now, we are integrating these platforms into both cancer immunology and patient therapy decision-making. Here, we briefly describe the technology platforms and highlight several emerging applications: profiling of tumor mutations and gene expression; determination of HLA type and tumor expression, enabling prediction of immunogenic tumor mutations; and identification of viruses present in tumors. These and other concepts will continue to expand the medical impact of NGS.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Adiconis X et al (2013) Comparative analysis of RNA sequencing methods for degraded or low-input samples. Nat Methods 10(7):623–629. doi:10.1038/nmeth.2483
Barretina J et al (2012) The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483(7391):603–607. doi:10.1038/nature11003
Boegel S et al (2013) HLA typing from RNA-Seq sequence reads. Genome Med 4(12):102. doi:10.1186/gm403
Britten CM et al (2013) The regulatory landscape for actively personalized cancer immunotherapies. Nat Biotechnol 31(10):880–882. doi:10.1038/nbt.2708
Castle JC et al (2012) Exploiting the mutanome for tumor vaccination. Cancer Res 72(5):1081–1091. doi:10.1158/0008-5472.CAN-11-3722
Chen Y et al (2013) VirusSeq: software to identify viruses and their integration sites using next-generation sequencing of human cancer tissue. Bioinformatics 29(2):266–267. doi:10.1093/bioinformatics/bts665
Cibulskis K et al (2013) Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat Biotechnol 31(3):213–219. doi:10.1038/nbt.2514
Cline MS et al (2013) Exploring TCGA Pan-Cancer data at the UCSC Cancer Genomics Browser. Sci Rep 3:2652. doi:10.1038/srep02652
Dawson SJ et al (2013) Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med 368(13):1199–1209. doi:10.1056/NEJMoa1213261
Diekmann J et al (2012) The T cell druggable genome. Eur Pharm Rev 17(4):16–19
Duenwald S et al (2009) Development of a microarray platform for FFPET profiling: application to the classification of human tumors. J Transl Med 7:65. doi:10.1186/1479–5876–7–65, 1479-5876-7-65 [pii]
Ellermann V, Bang O (1908) Experimentelle Leukämie bei Hühnern. Zentralbl Bakterielle Parasitkunde Abt I 46:595–609
Epstein MA et al (1964) Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet 1(7335):702–703
Forbes SA et al (2011) COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res 39(Database issue):D945–D950. doi:10.1093/nar/gkq929
Heitzer E et al (2013) Complex tumor genomes inferred from single circulating tumor cells by array-CGH and next-generation sequencing. Cancer Res 73(10):2965–2975. doi:10.1158/0008-5472.CAN-12-4140
Kandoth C et al (2013) Mutational landscape and significance across 12 major cancer types. Nature 502(7471):333–339. doi:10.1038/nature12634
Khoury JD et al (2013) Landscape of DNA virus associations across human malignant cancers: analysis of 3,775 cases using RNA-Seq. J Virol 87(16):8916–8926. doi:10.1128/JVI.00340-13
Kim HJ, Pourmand N (2013) HLA haplotyping from RNA-seq data using hierarchical read weighting. PLoS One 8(6):e67885. doi:10.1371/journal.pone.0067885
Kim Y et al (2011) Applications for T-cell epitope queries and tools in the Immune Epitope Database and Analysis Resource. J Immunol Methods 374(1–2):62–69. doi:10.1016/j.jim.2010.10.010
Koboldt DC et al (2012) VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res 22(3):568–576. doi:10.1101/gr.129684.111
Lander ES et al (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860–921
Li JW et al (2013) ViralFusionSeq: accurately discover viral integration events and reconstruct fusion transcripts at single-base resolution. Bioinformatics 29(5):649–651. doi:10.1093/bioinformatics/btt011
Liu C et al (2013) ATHLATES: accurate typing of human leukocyte antigen through exome sequencing. Nucleic Acids Res 41(14):e142. doi:10.1093/nar/gkt481
Lower M et al (2012) Confidence-based somatic mutation evaluation and prioritization. PLoS Comput Biol 8(9):e1002714. doi:10.1371/journal.pcbi.1002714
Metzker ML (2010) Sequencing technologies – the next generation. Nat Rev Genet 11(1):31–46. doi:10.1038/nrg2626
Moore PS, Chang Y (2010) Why do viruses cause cancer? Highlights of the first century of human tumour virology. Nat Rev Cancer 10(12):878–889. doi:10.1038/nrc2961
Peng X et al (2010) Unique signatures of long noncoding RNA expression in response to virus infection and altered innate immune signaling. MBio 1(5):e00206–10. doi:10.1128/mBio.00206-10
Robinson J et al (2013) The IMGT/HLA database. Nucleic Acids Res 41(Database issue):D1222–D1227. doi:10.1093/nar/gks949
Soderberg-Naucler C et al (2013) Survival in patients with glioblastoma receiving valganciclovir. N Engl J Med 369(10):985–986. doi:10.1056/NEJMc1302145
Sung WK et al (2012) Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma. Nat Genet 44(7):765–769. doi:10.1038/ng.2295
Tang KW et al (2013) The landscape of viral expression and host gene fusion and adaptation in human cancer. Nat Commun 4:2513. doi:10.1038/ncomms3513
Venter JC et al (2001) The sequence of the human genome. Science 291(5507):1304–1351. doi:10.1126/science.1058040
Wang C et al (2012) High-throughput, high-fidelity HLA genotyping with deep sequencing. Proc Natl Acad Sci U S A 109(22):8676–8681. doi:10.1073/pnas.1206614109
Wang Q et al (2013) VirusFinder: software for efficient and accurate detection of viruses and their integration sites in host genomes through next generation sequencing data. PLoS One 8(5):e64465. doi:10.1371/journal.pone.0064465
Warren RL et al (2012) Derivation of HLA types from shotgun sequence datasets. Genome Med 4(12):95. doi:10.1186/gm396
Westermann AJ et al (2012) Dual RNA-seq of pathogen and host. Nat Rev Microbiol 10(9):618–630. doi:10.1038/nrmicro2852
Wetterstrand KA (2013) DNA sequencing costs: data from the NHGRI Genome Sequencing Program (GSP). Available at: www.genome.gov/sequencingcosts. Accessed 28 Oct 2013
Yoshida K et al (2011) Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 478(7367):64–69. doi:10.1038/nature10496
Acknowledgment
We warmly thank Christoph Huber for his medical and scientific forethought, advice, guidance, mentorship, and friendship.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Castle, J.C., Boegel, S., Bukur, T., Boisguerin, V., Loewer, M. (2014). Genomics Meets Cancer Immunotherapy. In: Britten, C., Kreiter, S., Diken, M., Rammensee, HG. (eds) Cancer Immunotherapy Meets Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-05104-8_22
Download citation
DOI: https://doi.org/10.1007/978-3-319-05104-8_22
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-05103-1
Online ISBN: 978-3-319-05104-8
eBook Packages: MedicineMedicine (R0)