Supplementary Table S2. Summary of the studied , their related cellular pathways and the deregulated genes in the comparison of tumor to control tissue. UP UP DOWN DOWN Definition (Genecards) (P vs C) (R vs C) (P vs C) (R vs C) ALKBH2 AlkB Homolog 2, Alpha-Ketoglutarate Dependent Dioxygenase APEX1 Apurinic/Apyrimidinic Endo-deoxyribonuclease 1

ATM Ataxia Telangiectasia Mutated, ATM Serine/Threonine ATR Ataxia Telangiectasia And Rad3-Related , ATR Serine/Threonine kinase ATRX Alpha Thalassemia/Mental Retardation Syndrome X-Linked, Chromatin remodeler yes yes AURKA Aurora Kinase A yes yes AURKB Aurora Kinase B yes BLM RecQ Like yes yes BRCA1 Breast Type 1 Susceptibility Protein yes yes BRCA2 Type 2 Susceptibility Protein yes yes BRCC3 BRCA1/BRCA2-Containing Complex Subunit 3 BRIP1 BRCA1 Interacting Protein C-Terminal Helicase 1 yes yes

CCNA2 Cyclin A2 yes yes CCNB1 Cyclin B1 yes yes CCND1 Cyclin D1 CCND2 Cyclin D2 CCNE1 Cyclin E1 CDC25B Cell Division Cycle 25B yes yes CDC25C Cell Division Cycle 25C yes yes Cell Division Cycle 6 yes yes CDK1 Cyclin dependent kinase 1 yes yes CDK2 Cyclin dependent kinase 2 yes yes CDK4 Cyclin dependent kinase 4 yes yes CDK6 Cyclin dependent kinase 6 yes yes CDKN1A Cyclin Dependent Kinase Inhibitor 1A yes yes CENPA -Like Centromeric Protein A yes yes CENPB Centromere Protein B CENPF Centromere Protein F yes yes CHEK1 Checkpoint Kinase 1 yes yes CHEK2 Checkpoint Kinase 2 yes yes CUL4A Cullin 4A DCLRE1A DNA Cross-Link Repair 1A yes yes DCLRE1C DNA Cross-Link Repair 1C, Artemis DDB1 Damage Specific DNA Binding Protein 1 yes yes DDB2 Damage Specific DNA Binding Protein 2 yes DSN1 DSN1 Homolog, MIS12 Complex Component yes

EME1 Essential Meiotic Structure-Specific Endonuclease 1 yes yes ERCC1 Excision Repair Cross-Complementation Group 1 ERCC2 ERCC Excision Repair 2, TFIIH Core Complex Helicase Subunit ERCC3 ERCC Excision Repair 3, TFIIH Core Complex Helicase Subunit yes yes

ERCC4 ERCC Excision Repair 4, Endonuclease Catalytic Subunit ERCC5 ERCC Excision Repair 5, Endonuclease yes yes ERCC6 ERCC Excision Repair 6, Factor yes yes FAAP24 Core Complex Associated Protein 24 yes FANCA Fanconi Anemia Complementation Group A yes yes FANCD2 Fanconi Anemia Complementation Group D2 yes yes FANCF Fanconi Anemia Complementation Group F FANCL Fanconi Anemia Complementation Group L yes yes FANCM Fanconi Anemia Complementation Group M FEN1 Flap Structure-Specific Endonuclease 1 GADD45G Growth Arrest And DNA Damage Inducible Gamma GRN Granulin Precursor yes yes HMMR Hyaluronan Mediated Motility Receptor yes yes HUS1 HUS1 Checkpoint Clamp Component PCLAF PCNA Clamp Associated Factor yes yes LIG1 DNA Ligase 1 LIG3 DNA Ligase 3 LIG4 DNA Ligase 4 yes yes MAD2L2 Mitotic Arrest Deficient-Like Protein 2 yes MBD4 Methyl-CpG Binding Domain 4, DNA Glycosylase MCM2 Minichromosome Maintenance Complex Component 2 yes yes MCM3 Minichromosome Maintenance Complex Component 3 yes yes MCM7 Minichromosome Maintenance Complex Component 7 yes yes MGMT O-6-Methylguanine-DNA Methyltransferase yes yes MKI67 Marker Of Proliferation Ki-67 yes yes MLH1 MutL Homolog 1 MLH3 MutL Homolog 3 yes yes MMS19 MMS19 Homolog, Cytosolic Iron-Sulfur Assembly Component yes yes MPG N-Methylpurine DNA Glycosylase MRE11A Meiotic Recombination 11 Homolog, Double Strand Break Repair Nuclease MSH2 MutS Homolog 2 yes yes MSH3 MutS Homolog 3 yes yes MSH6 MutS Homolog 6 MUS81 SLX3 Structure-Specific Endonuclease Subunit Homolog MUTYH MutY DNA Glycosylase homolog

NBN Nijmegen Breakage Syndrome 1 NEIL1 Nei Like DNA Glycosylase 1 yes yes NEIL2 Nei Like DNA Glycosylase 2 yes yes NEIL3 Nei Like DNA Glycosylase 3 yes yes NHEJ1 Non-Homologous End Joining Factor 1 NSMCE2 Non-Structural Maintenance Of Element 2 Homolog NUDT1 Nudix Hydrolase 1 yes yes OGG1 8-Oxoguanine DNA Glycosylase PALB2 Partner And Localizer Of BRCA2 PARG Poly(ADP-Ribose) Glycohydrolase yes yes PARP1 Poly(ADP-Ribose) 1 PCNA Proliferating Cell Nuclear Antigen yes yes PLK1 Polo Like Kinase 1 yes yes PMS1 PMS1 Homolog 1, Mismatch Repair System Component PMS2 PMS1 Homolog 2, Mismatch Repair System Component yes yes POLB DNA Polymerase Beta yes yes POLD1 DNA Polymerase Delta 1, Catalytic Subunit yes yes POLH DNA Polymerase Eta POLK DNA Polymerase Kappa POLL DNA Polymerase Lambda yes yes POLM DNA Polymerase Mu yes POLQ DNA Polymerase Theta yes yes PRIM1 (DNA) Subunit 1 PRKDC , DNA-Activated, Catalytic Polypeptide PSMD14 26S Subunit, Non-ATPase 14 PTEN Phosphatase And Tensin Homolog yes yes PTTG1 Pituitary Tumor-Transforming 1 yes yes RAD1 Rad1-Like DNA Damage Checkpoint Protein RAD17 RAD17 Checkpoint Clamp Loader Component RAD18 RAD18, E3 Protein Ligase yes yes RAD23A RAD23 Homolog A, Nucleotide Excision Repair Protein RAD23B RAD23 Homolog B, Nucleotide Excision Repair Protein RAD50 RAD50 Double Strand Break Repair Protein yes yes RAD51 RAD51 Recombinase yes yes RAD52 RAD52 Homolog, DNA Repair Protein RAD54B RAD54 Homolog B RAD54L RAD54-Like yes yes RAD9A RAD9 Checkpoint Clamp Component A RBM14 RNA Binding Motif Protein 14 RDM1 RAD52 Motif Containing 1 RECQL RecQ Like Helicase yes yes RECQL4 RecQ Like Helicase 4 RECQL5 RecQ Like Helicase 5 REV1 REV1, DNA Directed Polymerase REV3L REV3 Like, DNA Directed Polymerase Zeta Catalytic Subunit RFC1 Subunit 1 RFC2 Replication Factor C Subunit 2 yes RFC3 Replication Factor C Subunit 3 RFC4 Replication Factor C Subunit 4 yes yes RNF168 Ring Finger Protein 168 RNF4 Ring Finger Protein 4 RNF8 Ring Finger Protein 8, E3 Ubiquitin Protein Ligase yes yes RPA1 RPA2 RPA3 RRM1 Ribonucleotide Reductase Catalytic Subunit M1 SEM1 SEM1, 26S Proteasome Complex Subunit SMC3 Structural Maintenance Of Chromosomes 3 SMUG1 Single-Strand-Selective Monofunctional Uracil-DNA Glycosylase 1 TERT yes TOP2A (DNA) II Alpha yes yes TP53BP1 Tumor Protein Binding Protein 1 yes yes TUBG1 Gamma 1 UBE2I Ubiquitin Conjugating E2 I UBE2T Ubiquitin Conjugating Enzyme E2 T UBE3B Ubiquitin Protein Ligase E3B yes yes UIMC1 Ubiquitin Interaction Motif Containing 1 UNG Uracil DNA Glycosylase USP1 Ubiquitin Specific Peptidase 1 USP47 Ubiquitin Specific Peptidase 47 XPA Xeroderma Pigmentosum Group A-Complementing Protein yes XPC Xeroderma Pigmentosum, Complementation Group C XRCC1 X-Ray Repair Cross Complementing 1 XRCC2 X-Ray Repair Cross Complementing 2 yes yes XRCC3 X-Ray Repair Cross Complementing 3 XRCC4 X-Ray Repair Cross Complementing 4 XRCC5 X-Ray Repair Cross Complementing 5 XRCC6 X-Ray Repair Cross Complementing 6 XRCC6BP1 XRCC6-Binding Protein 1

Supplementary Table S3. Univariate Cox regression analysis of factors influencing PFS and OS in the Köln patient cohort. p-value Variable Category PFS OS Age Continuous 0.612 0.457 Gender Male 0.435 0.255 Female KPS Continous 0.587 0.169 MGMT status Un-methylated 0.527 0.918 Methylated Groups (signature specific) G1 0.019 0.132 G3 KPS, Karnofsky performance score; PFS, progression free survival; OS, overall survival