Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Radiation Oncology
Published in: Radiation Oncology 1/2015

Open Access 01-12-2015 | Review

Next-generation sequencing: hype and hope for development of personalized radiation therapy?

Authors: Ingeborg Tinhofer, Franziska Niehr, Robert Konschak, Sandra Liebs, Matthias Munz, Albrecht Stenzinger, Wilko Weichert, Ulrich Keilholz, Volker Budach

Published in: Radiation Oncology | Issue 1/2015

Login to get access

Abstract

The introduction of next-generation sequencing (NGS) in the field of cancer research has boosted worldwide efforts of genome-wide personalized oncology aiming at identifying predictive biomarkers and novel actionable targets. Despite considerable progress in understanding the molecular biology of distinct cancer entities by the use of this revolutionary technology and despite contemporaneous innovations in drug development, translation of NGS findings into improved concepts for cancer treatment remains a challenge. The aim of this article is to describe shortly the NGS platforms for DNA sequencing and in more detail key achievements and unresolved hurdles. A special focus will be given on potential clinical applications of this innovative technique in the field of radiation oncology.
Literature
1.
Ciriello G, Miller ML, Aksoy BA, Senbabaoglu Y, Schultz N, Sander C. Emerging landscape of oncogenic signatures across human cancers. Nat Genet. 2013;45(10):1127–33.PubMedCentralCrossRefPubMed
2.
Meyerson M, Gabriel S, Getz G. Advances in understanding cancer genomes through second-generation sequencing. Nat Rev Genet. 2010;11(10):685–96.CrossRefPubMed
3.
Tamborero D, Gonzalez-Perez A, Perez-Llamas C, Deu-Pons J, Kandoth C, Reimand J, et al. Comprehensive identification of mutational cancer driver genes across 12 tumor types. Sci Rep. 2013;3:2650.PubMedCentralPubMed
4.
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(7457):214–8.PubMedCentralCrossRefPubMed
5.
Ku CS, Naidoo N, Wu M, Soong R. Studying the epigenome using next generation sequencing. J Med Genet. 2011;48(11):721–30.CrossRefPubMed
6.
7.
Morozova O, Hirst M, Marra MA. Applications of new sequencing technologies for transcriptome analysis. Annu Rev Genomics Hum Genet. 2009;10:135–51.CrossRefPubMed
8.
9.
Derks KW, Misovic B, van den Hout MC, Kockx CE, Gomez CP, Brouwer RW, et al. Deciphering the RNA landscape by RNAome sequencing. RNA Biol. 2015;12(1):30–42.CrossRefPubMed
10.
11.
Wong KM, Hudson TJ, McPherson JD. Unraveling the genetics of cancer: genome sequencing and beyond. Annu Rev Genomics Hum Genet. 2011;12:407–30.CrossRefPubMed
12.
Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409(6822):860–921.CrossRefPubMed
13.
McPherson JD, Marra M, Hillier L, Waterston RH, Chinwalla A, Wallis J, et al. A physical map of the human genome. Nature. 2001;409(6822):934–41.CrossRefPubMed
14.
Sachidanandam R, Weissman D, Schmidt SC, Kakol JM, Stein LD, Marth G, et al. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature. 2001;409(6822):928–33.CrossRefPubMed
15.
16.
Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature. 2009;461(7261):272–6.PubMedCentralCrossRefPubMed
17.
Simon R, Roychowdhury S. Implementing personalized cancer genomics in clinical trials. Nat Rev Drug Discov. 2013;12(5):358–69.CrossRefPubMed
18.
Kriegsmann M, Endris V, Wolf T, Pfarr N, Stenzinger A, Loibl S, et al. Mutational profiles in triple-negative breast cancer defined by ultradeep multigene sequencing show high rates of PI3K pathway alterations and clinically relevant entity subgroup specific differences. Oncotarget. 2014;5(20):9952–65.PubMedCentralPubMed
19.
Hedegaard J, Thorsen K, Lund MK, Hein AM, Hamilton-Dutoit SJ, Vang S, et al. Next-generation sequencing of RNA and DNA isolated from paired fresh-frozen and formalin-fixed paraffin-embedded samples of human cancer and normal tissue. PLoS One. 2014;9(5):e98187.PubMedCentralCrossRefPubMed
20.
Lebofsky R, Decraene C, Bernard V, Kamal M, Blin A, Leroy Q, et al. Circulating tumor DNA as a non-invasive substitute to metastasis biopsy for tumor genotyping and personalized medicine in a prospective trial across all tumor types. Mol Oncol. 2015;9(4):783–90.CrossRefPubMed
21.
Sanger F, Coulson AR. A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol. 1975;94(3):441–8.CrossRefPubMed
22.
Johansson H, Isaksson M, Sorqvist EF, Roos F, Stenberg J, Sjoblom T, et al. Targeted resequencing of candidate genes using selector probes. Nucleic Acids Res. 2011;39(2):e8.PubMedCentralCrossRefPubMed
23.
Bodi K, Perera AG, Adams PS, Bintzler D, Dewar K, Grove DS, et al. Comparison of commercially available target enrichment methods for next-generation sequencing. J Biomol Tech. 2013;24(2):73–86.PubMedCentralPubMed
24.
Belkadi A, Bolze A, Itan Y, Cobat A, Vincent QB, Antipenko A, et al. Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variants. Proc Natl Acad Sci U S A. 2015;112(17):5473–8.CrossRefPubMed
25.
Genomes Project C, Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, et al. A map of human genome variation from population-scale sequencing. Nature. 2010;467(7319):1061–73.CrossRef
26.
Forbes SA, Beare D, Gunasekaran P, Leung K, Bindal N, Boutselakis H, et al. COSMIC: exploring the world’s knowledge of somatic mutations in human cancer. Nucleic Acids Res. 2015;43(Database issue):D805–11.PubMedCentralCrossRefPubMed
27.
28.
Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc. 2009;4(7):1073–81.CrossRefPubMed
29.
Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7(4):248–9.PubMedCentralCrossRefPubMed
30.
Reva B, Antipin Y, Sander C. Predicting the functional impact of protein mutations: application to cancer genomics. Nucleic Acids Res. 2011;39(17):e118.PubMedCentralCrossRefPubMed
31.
Getz G, Hofling H, Mesirov JP, Golub TR, Meyerson M, Tibshirani R, et al. Comment on “The consensus coding sequences of human breast and colorectal cancers”. Science. 2007;317(5844):1500.CrossRefPubMed
32.
33.
Schott AF, Perou CM, Hayes DF. Genome Medicine in Cancer: What’s in a Name? Cancer Res. 2015;75(10):1930–5.CrossRefPubMed
34.
Pouliliou SE, Lialiaris TS, Dimitriou T, Giatromanolaki A, Papazoglou D, Pappa A, et al. Survival Fraction at 2 Gy and gammaH2AX Expression Kinetics in Peripheral Blood Lymphocytes From Cancer Patients: Relationship With Acute Radiation-Induced Toxicities. Int J Radiat Oncol Biol Phys. 2015;92(3):667–74.CrossRefPubMed
35.
Menegakis A, Eicheler W, Yaromina A, Thames HD, Krause M, Baumann M. Residual DNA double strand breaks in perfused but not in unperfused areas determine different radiosensitivity of tumours. Radiother Oncol. 2011;100(1):137–44.CrossRefPubMed
36.
van Waarde MA, van Assen AJ, Konings AW, Kampinga HH. Feasibility of measuring radiation-induced DNA double strand breaks and their repair by pulsed field gel electrophoresis in freshly isolated cells from the mouse RIF-1 tumor. Int J Radiat Oncol Biol Phys. 1996;36(1):125–34.CrossRefPubMed
37.
Rube CE, Grudzenski S, Kuhne M, Dong X, Rief N, Lobrich M, et al. DNA double-strand break repair of blood lymphocytes and normal tissues analysed in a preclinical mouse model: implications for radiosensitivity testing. Clin Cancer Res. 2008;14(20):6546–55.CrossRefPubMed
38.
Zips D, Eicheler W, Bruchner K, Jackisch T, Geyer P, Petersen C, et al. Impact of the tumour bed effect on microenvironment, radiobiological hypoxia and the outcome of fractionated radiotherapy of human FaDu squamous-cell carcinoma growing in the nude mouse. Int J Radiat Biol. 2001;77(12):1185–93.CrossRefPubMed
39.
Eschrich S, Zhang H, Zhao H, Boulware D, Lee JH, Bloom G, et al. Systems biology modeling of the radiation sensitivity network: a biomarker discovery platform. Int J Radiat Oncol Biol Phys. 2009;75(2):497–505.PubMedCentralCrossRefPubMed
40.
Eschrich SA, Fulp WJ, Pawitan Y, Foekens JA, Smid M, Martens JW, et al. Validation of a radiosensitivity molecular signature in breast cancer. Clin Cancer Res. 2012;18(18):5134–43.PubMedCentralCrossRefPubMed
41.
Toustrup K, Sorensen BS, Lassen P, Wiuf C, Alsner J, Overgaard J, et al. Gene expression classifier predicts for hypoxic modification of radiotherapy with nimorazole in squamous cell carcinomas of the head and neck. Radiother Oncol. 2012;102(1):122–9.CrossRefPubMed
42.
Hassan Metwally MA, Ali R, Kuddu M, Shouman T, Strojan P, Iqbal K, et al. IAEA-HypoX. A randomized multicenter study of the hypoxic radiosensitizer nimorazole concomitant with accelerated radiotherapy in head and neck squamous cell carcinoma. Radiother Oncol. 2015.
43.
Teo MT, Dyrskjot L, Nsengimana J, Buchwald C, Snowden H, Morgan J, et al. Next-generation sequencing identifies germline MRE11A variants as markers of radiotherapy outcomes in muscle-invasive bladder cancer. Ann Oncol. 2014;25(4):877–83.PubMedCentralCrossRefPubMed
44.
Harris DR, Pollock SV, Wood EA, Goiffon RJ, Klingele AJ, Cabot EL, et al. Directed evolution of ionizing radiation resistance in Escherichia coli. J Bacteriol. 2009;191(16):5240–52.PubMedCentralCrossRefPubMed
45.
Tinhofer I, Budach V, Endris V, Stenzinger A, Weichert W. Genomic profiling using targeted ultra-deep next-generation sequencing for prediction of treatment outcome after concurrent chemoradiation: Results from the German ARO-0401 trial. J Clin Oncol. 2014;32(5s):abstr 6002.
46.
Tinhofer I, Budach V, Linge A, Lohaus F, Gkika E, Stuschke M, et al. Mutational patterns of HPV+ and HPV- squamous cell carcinomas of the head and neck (SCCHN) and their interference with outcome after adjuvant chemoradiation: A multicenter biomarker study of the German Cancer Consortium Radiation Oncology Group. J Clin Oncol. 2015;33(5s):abstr 6006.
47.
Lindenbergh-van der Plas M, Brakenhoff RH, Kuik DJ, Buijze M, Bloemena E, Snijders PJ, et al. Prognostic significance of truncating TP53 mutations in head and neck squamous cell carcinoma. Clin Cancer Res. 2011;17(11):3733–41.CrossRefPubMed
48.
Skinner HD, Sandulache VC, Ow TJ, Meyn RE, Yordy JS, Beadle BM, et al. TP53 disruptive mutations lead to head and neck cancer treatment failure through inhibition of radiation-induced senescence. Clin Cancer Res. 2012;18(1):290–300.PubMedCentralCrossRefPubMed
49.
Sakai K, Kazama S, Nagai Y, Murono K, Tanaka T, Ishihara S, et al. Chemoradiation provides a physiological selective pressure that increases the expansion of aberrant TP53 tumor variants in residual rectal cancerous regions. Oncotarget. 2014;5(20):9641–9.PubMedCentralPubMed
50.
Rodriguez OC, Choudhury S, Kolukula V, Vietsch EE, Catania J, Preet A, et al. Dietary downregulation of mutant p53 levels via glucose restriction: mechanisms and implications for tumor therapy. Cell Cycle. 2012;11(23):4436–46.PubMedCentralCrossRefPubMed
51.
Bykov VJ, Issaeva N, Selivanova G, Wiman KG. Mutant p53-dependent growth suppression distinguishes PRIMA-1 from known anticancer drugs: a statistical analysis of information in the National Cancer Institute database. Carcinogenesis. 2002;23(12):2011–8.CrossRefPubMed
52.
Hu J, Adar S, Selby CP, Lieb JD, Sancar A. Genome-wide analysis of human global and transcription-coupled excision repair of UV damage at single-nucleotide resolution. Genes Dev. 2015;29(9):948–60.CrossRefPubMed
53.
Burnette B, Weichselbaum RR. Radiation as an immune modulator. Semin Radiat Oncol. 2013;23(4):273–80.CrossRefPubMed
54.
Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol. 2013;31:51–72.CrossRefPubMed
55.
Brown SD, Warren RL, Gibb EA, Martin SD, Spinelli JJ, Nelson BH, et al. Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival. Genome Res. 2014;24(5):743–50.PubMedCentralCrossRefPubMed
56.
Binder DC, Fu YX, Weichselbaum RR. Radiotherapy and immune checkpoint blockade: potential interactions and future directions. Trends Mol Med. 2015
57.
Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, et al. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415–21.PubMedCentralCrossRefPubMed
58.
Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 2011;333(6046):1154–7.PubMedCentralCrossRefPubMed
59.
Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011;333(6046):1157–60.PubMedCentralCrossRefPubMed
60.
The Cancer Genome Atlas N. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517(7536):576–82.CrossRef
61.
62.
Wood LD, Parsons DW, Jones S, Lin J, Sjoblom T, Leary RJ, et al. The genomic landscapes of human breast and colorectal cancers. Science. 2007;318(5853):1108–13.CrossRefPubMed
63.
Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366(10):883–92.CrossRefPubMed
64.
65.
de Bruin EC, McGranahan N, Mitter R, Salm M, Wedge DC, Yates L, et al. Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science. 2014;346(6206):251–6.CrossRefPubMed
66.
Baldus SE, Schaefer KL, Engers R, Hartleb D, Stoecklein NH, Gabbert HE. Prevalence and heterogeneity of KRAS, BRAF, and PIK3CA mutations in primary colorectal adenocarcinomas and their corresponding metastases. Clin Cancer Res. 2010;16(3):790–9.CrossRefPubMed
67.
Kreso A, O’Brien CA, van Galen P, Gan OI, Notta F, Brown AM, et al. Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer. Science. 2013;339(6119):543–8.CrossRefPubMed
68.
Navin N, Kendall J, Troge J, Andrews P, Rodgers L, McIndoo J, et al. Tumour evolution inferred by single-cell sequencing. Nature. 2011;472(7341):90–4.PubMedCentralCrossRefPubMed
69.
Meier B, Cooke SL, Weiss J, Bailly AP, Alexandrov LB, Marshall J, et al. C. elegans whole-genome sequencing reveals mutational signatures related to carcinogens and DNA repair deficiency. Genome Res. 2014;24(10):1624–36.PubMedCentralCrossRefPubMed
70.
Munoz EF, Diwan BA, Calvert RJ, Weghorst CM, Anderson J, Rice JM, et al. Transplacental mutagenicity of cisplatin: H-ras codon 12 and 13 mutations in skin tumors of SENCAR mice. Carcinogenesis. 1996;17(12):2741–5.CrossRefPubMed
71.
Cho HJ, Jeong HG, Lee JS, Woo ER, Hyun JW, Chung MH, et al. Oncogenic H-Ras enhances DNA repair through the Ras/phosphatidylinositol 3-kinase/Rac1 pathway in NIH3T3 cells. Evidence for association with reactive oxygen species. J Biol Chem. 2002;277(22):19358–66.CrossRefPubMed
72.
Gonin-Laurent N, Gibaud A, Huygue M, Lefevre SH, Le Bras M, Chauveinc L, et al. Specific TP53 mutation pattern in radiation-induced sarcomas. Carcinogenesis. 2006;27(6):1266–72.CrossRefPubMed
73.
Wade MA, Sunter NJ, Fordham SE, Long A, Masic D, Russell LJ, et al. c-MYC is a radiosensitive locus in human breast cells. Oncogene. 2014.
74.
Forshew T, Murtaza M, Parkinson C, Gale D, Tsui DW, Kaper F, et al. Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. Sci Transl Med. 2012;4(136):136ra68.CrossRefPubMed
75.
Dawson SJ, Tsui DW, Murtaza M, Biggs H, Rueda OM, Chin SF, et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013;368(13):1199–209.CrossRefPubMed
76.
Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6(224):224ra24.PubMedCentralCrossRefPubMed
77.
Newman AM, Bratman SV, To J, Wynne JF, Eclov NC, Modlin LA, et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med. 2014;20(5):548–54.PubMedCentralCrossRefPubMed
78.
Frenel JS, Carreira S, Goodall J, Roda Perez D, Perez Lopez R, Tunariu N, et al. Serial Next Generation Sequencing of Circulating Cell Free DNA Evaluating Tumour Clone Response To Molecularly Targeted Drug Administration. Clin Cancer Res. 2015.
79.
Martinez Molina D, Jafari R, Ignatushchenko M, Seki T, Larsson EA, Dan C, et al. Monitoring drug target engagement in cells and tissues using the cellular thermal shift assay. Science. 2013;341(6141):84–7.CrossRefPubMed
80.
Savitski MM, Reinhard FB, Franken H, Werner T, Savitski MF, Eberhard D, et al. Tracking cancer drugs in living cells by thermal profiling of the proteome. Science. 2014;346(6205):1255784.CrossRefPubMed
Metadata
Title
Next-generation sequencing: hype and hope for development of personalized radiation therapy?
Authors
Ingeborg Tinhofer
Franziska Niehr
Robert Konschak
Sandra Liebs
Matthias Munz
Albrecht Stenzinger
Wilko Weichert
Ulrich Keilholz
Volker Budach
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2015
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-015-0481-x

Other articles of this Issue 1/2015

Radiation Oncology 1/2015 Go to the issue

Research

Dexamethasone administration during definitive radiation and temozolomide renders a poor prognosis in a retrospective analysis of newly diagnosed glioblastoma patients

Research

Dosimetric comparison of carbon ion radiotherapy and stereotactic body radiotherapy with photon beams for the treatment of hepatocellular carcinoma

Review

Current state of the art of regional hyperthermia treatment planning: a review

Short report

Effect of prostate-specific membrane antigen positron emission tomography on the decision-making of radiation oncologists

Research

Analysis of motion of the rectum during preoperative intensity modulated radiation therapy for rectal cancer using cone-beam computed tomography

Research

Evaluating organ delineation, dose calculation and daily localization in an open-MRI simulation workflow for prostate cancer patients