EGAGenomicsCancer Genomicshttps://ega-archive.org/studies/EGAS00001004320EGAEGA study EGAS00001004320Whole exome data from PMID27216186EGArestrictedlod, WES, WHOLE EXOME SEQUENCING, DmelCG2684, WXS (whole exome sequencing), developmental stage, Exome, familial, WXS, Evolution, NTef2, Lds, early, Fs(3)Sz11, genetic, Exome Sequencing, Horka, heterogeneity, Whole Exome Sequencing, CG2684, Fs(3)Horka, inherited genetic, stage, DmF2, metastatic melanoma, metastatic malignant melanoma., constitutitional genetic, Fs(3)Hor, hereditary, Whole-Exome SequencingUVO Gene Mutation, Anti-HBsAb Positive, Beta Gene Mutation, H. pylori Positive, degree (angle), RNA Sequence Determination, RNA-seq (transcriptome sequencing), Sequence Determination, RNA Sequence, Addresses, Progesterone Receptor Positive, Visible Light, growth and development, Progress Reports, Tumor, FGFBR Gene Rearrangement, ERBB2 Amplification, Mutations, Positive Charge, UVB radiation, RET/PTC Rearrangement, Hepatitis C Virus RNA Positive, p53 Mutation, sequencing assay, PGR Positive, Summary Report, Nuclear Receptor Subfamily 3 Group A Member 1 Positive, Transcriptome Sequencing, AA120551, Analysis, Fs(3)Hor, Erg-3 Gene Rearrangement, CD332 Gene Mutation, Ha-ras Gene Mutation, Gene Variation Not Detected, Progression, Methylated MGMT Promoter, EXPRESSED, HRas Proto-Oncogene, ERA Positive, Biopsies, G Protein Subunit Alpha q Gene Mutation, Genomes, Analyses, Progress Report, IDH Gene Mutation, CD324 Gene Mutation, TRT Promoter Mutation, ClinicalHistory, proportionality to, Hepatitis B Virus Core Antibody Positive, c-KIT Positive, result, Flavoprotein Subunit of Complex II Positive, GAQ Gene Mutation, Met Proto-Oncogene (Hepatocyte Growth Factor Receptor) Gene Amplification, B7H1 Positive, BEK Gene Mutation, FGFR1 Gene Rearrangement, {EVENTS}, node-positive, Cadherin 1 Gene Mutation, NTef2, Evolution, PD-L1+, Sequence Determinations, ESTRB Positive, Based, XH2 Gene Mutation, Did, DID, NEU Gene Mutation, Mutation Abnormality, v-raf Murine Sarcoma Viral Oncogene Homolog B1 Gene Rearrangement, Catenin Beta 1 Gene Mutation, Field Reports, FGFR3 Gene Mutation, ER Beta Positive, SDHB Positive, Familiar, K-RAS Mutation, CD331 Gene Rearrangement, C-HA-RAS1 Gene Mutation, Telomerase Reverse Transcriptase Gene Promoter Mutation, MET Amplification, ZNF-HX Gene Mutation, Comprehensive, Methylated MGMT Gene Promoter, ERBB2 Gene Amplification, Tumors, Beta Catenin Gene Mutation, Add, RES, sequencing_assay, Radiation, anatomical protrusion, Human Immunodeficiency Virus Positive, KGFR Gene Rearrangement, Difference, UNQ391/PRO726, c-erbB2 Gene Amplification, familial, B-RAF Gene Rearrangement, Anti-HBc Positive, Gene Mutation Detected, Light, Malignant Melanomas, historical aspects, Hepatitis B Virus Surface Antibody Positive, Estrogen Receptor Alpha Positive, Fs(3)Sz11, Alpha 11 Gene Mutation, Electrical Current, CD331 Gene Mutation, Benign, LIGHT, ERB Positive, SDHIP Positive, Do, Cadherin, Tumor Progression, CURRENT, Disease Progression, Gene Variation Negative, Genetic Alteration, JKT4 Gene Rearrangement, FGFR-2 Gene Rearrangement, FLT2 Gene Mutation, FGFR-1 Gene Rearrangement, RET Gene Rearrangement, CMC1 Gene Mutation, NRAS Gene Mutation, P53 Gene Mutation, HVEML, ECAD Gene Mutation, Cancer Disease Progression, Guanine Nucleotide-Binding Protein, PAX8 Gene Rearrangement, NR3A1 Positive, Very Low, proportionality, Field, NRAS, Benign Neoplasms, rate, Keratinocyte Growth Factor Receptor Gene Rearrangement, whole genome, HER2 Amplification, EST2 Promoter Mutation, Present, ESR Positive, PDCD1L1 Positive, Malignant Neoplasms, CD333 Gene Mutation, Positive Epstein-Barr Virus Test, Report, Positive EBV Serum Test, IDH Gene Family Mutation, historical notes, RNAseq, Whole-Transcriptome Sequencing, FGFBR Gene Mutation, N-RAS Gene Mutation, HER2/Neu Amplification, Ultraviolet-B Radiation, CG2684, WHOLE TRANSCRIPTOME SEQUENCING, TCS1 Promoter Mutation, KRAS Gene Mutation, Passive Double Immunodiffusion, Expression of PD-L1, other neoplasm, UVB Radiation, AA473386, BFGFR Gene Mutation, Induced, whole exome, Proficiency Testing Challenge, SDHF Positive, Nuclear Receptor Subfamily 3 Group A Member 2 Positive, Aspect, BRCA1-Associated Protein 1 Gene Mutation, Neoplasms, CDHE Gene Mutation, Different, HCV RNA Positive, Succinate Dehydrogenase [Ubiquinone] Iron-Sulfur Subunit, Hepatitis B Virus Surface Antigen Positive, ER+, Ly113, Inducible, Receptor Tyrosine Kinase Gene Amplification, melanoma (disease), FGFR1 Gene Mutation, Biopolymer Sequencing, p55 Gene Rearrangement, FLG Gene Rearrangement, PDCD1LG1 Positive, ALPS4, mutation, G Protein Subunit Alpha 11 Gene Mutation, Gene Variant Positive, B7-H Positive, ETV Rearrangement, androgen receptor positive, Cadherin-Associated Protein, proportion, Negation, In, HBs Positive, Clinical, Supply, MGMT Gene Methylation, Positive Number, disease progression, Hepatitis B Core Antibody Positive, Observation Result., Naevocarcinoma, Inducing, C87398, Events, positive test result, v-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog Gene Mutation, GNAQ Gene Mutation, Sequencing, intratumoral, PD-L1 Positive, outcome, BEK Gene Rearrangement, Neoplasias, RET Rearrangement, CTNNB1 Gene Mutation, PERFORMED, FGFR2 Gene Rearrangement, Clinical Course, Supplied, RAD54 Homolog Gene Mutation, ANO1 Positive, Gene Variation Detected, RAD54 Gene Mutation, Not Mutated, TR2, RNA-Seq, Expression, HER-2 Gene Amplification, Investigative Reports, constitutitional genetic, metastatic malignant melanoma, Cancer, Sequence Analyses, CD117 Positive, FGFR2 Gene Mutation, Positive EBV Test, SINGLE, Perform, RNA, Malignant Neoplasm, Helicobacter pylori Positive, NRAS1, RNA Sequence Determinations, PR Positive, ESRB Positive, Result, Hepatitis B Surface Protein Antigen Positive, BRAF1, Estrogen Receptor Positive, Frequently, CD258, Conclusion, B-RAF1 Gene Rearrangement, Addition, Positive Finding, Genetic Change, MT, ATRX, BRAF Gene Rearrangement, GNA11 Gene Mutation, Malignant Melanoma, Research Reports, Neoplasm, Expression Positive, FLG Gene Mutation, PAX8 Rearrangement, Approach, Androgen Receptor Positive, Induce, HGFR Gene Amplification, Hepatocyte Growth Factor Receptor Gene Amplification, ESR1 Positive, Mutation, MET Gene Amplification, c-MET Gene Amplification, UVB, ER-Alpha Positive, ultraviolet B radiation, Single Person, primary cancer, Methylated MGMT, progression, HBcAb Positive, HVEM-L, de-identification, ERG Rearrangement, Carcinogeneses, Tumor Protein p53 Gene Mutation, postnatal growth, HBsAg Positive, WTSS, IPSS-R Very Low Risk, Cancers, IP Positive, Hepatitis B Surface Antigen Positive, Lds, Negated, malignant tumor, TERT Gene Promoter Mutation, N-RAS Mutation, FLT-2 Gene Mutation, No, ETS Transcription Factor ERG Gene Rearrangement, Ret Proto-Oncogene Rearrangement, Differential, Photoradiations, Reports, Braf2, IDH Mutation, CEK Gene Mutation, 1p/19q Co-deletion, quotient, SDHA Positive, Solitary, Q Polypeptide Gene Mutation, Occurrence Indicator, Alpha-11 Gene Mutation, biopsy, Succinate Dehydrogenase [Ubiquinone] Flavoprotein Subunit, hereditary, Chromatin Remodeler Gene Mutation, Double Immunodiffusion, Neoplasia, Alone, Estrogen Receptor 2 Positive, mRNA Expression, XNP Gene Mutation, O-6-Methylguanine-DNA Methyltransferase Gene Promoter Methylation, Fibroblast Growth Factor Receptor 1 Gene Mutation, ER Positive, single-organism developmental process, v-Ets Erythroblastosis Virus E26 Oncogene Like Gene Rearrangement, Frequent, postnatal development, Expression Detected, Hepatitis C Viral RNA Positive, FLT-2 Gene Rearrangement, JKT4 Gene Mutation, AR+, KRAS Mutation, protein expression, HRAS1 Gene Mutation, G-ALPHA-q Gene Mutation, BAP1 Gene Mutation, ESR-Beta Positive, Fibroblast Growth Factor Receptor 2 Gene Rearrangement, FGFR-3 Gene Rearrangement, melanoma, Underlying, cytopathology, KGFR Gene Mutation, Very Low Risk, v-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2 Gene Mutation, Summary Reports, TP53, Abnormal, gene expression, NCMS, estrogen receptor positive, Total RNA Sequencing, N-ras, DmelCG2684, Estrogen Receptor Beta Positive, Protein Expression, Gene Mutation Negative, Determination, Whole Transcriptome Sequencing, Provide, DOG1 Positive, Alpha Thalassemia/Mental Retardation Syndrome X-Linked Gene Mutation, Oncogeneses, Histories, ETV Family Gene Rearrangement, Ets Variant Family Rearrangement, FLT2 Gene Rearrangement, Occurred, 9930012E13Rik, genetic, Rearrangement identified, Progress, TNFSF14, FGFR3 Gene Rearrangement, c-Met Gene Amplification, ECT1 Gene Mutation, Estrogen Receptor 1 Positive, C230098H17, PR+, FMS-Like Tyrosine Kinase 2 Gene Rearrangement, Fibroblast Growth Factor Receptor 2 Gene Mutation, malignant neoplasm, IDH Family Mutation, CDISC Events Class, CD333 Gene Rearrangement, Anti-Hepatitis B Core Antibody Positive, B7 Homolog 1 Positive, Exacerbation, Event Unit, Beta 1 (88kD) Gene Mutation, Allele, Malignancies, D6Ertd631e, Positive, Outcome, ATRX Gene Mutation, ERG Gene Rearrangement, B-RAF1, Anti-HBs Antibody Positive, TP53 Gene Mutation, Disease Exacerbation, 1p/19q co-deletion, KIT Proto-Oncogene Tyrosine Protein Kinase Positive, v-Ha-ras Harvey Rat Sarcoma Viral Oncogene Homolog Gene Mutation, HER2 Gene Mutation, somatic, Positive Estrogen Receptor, Determinations, HBsAb Positive, K-SAM Gene Mutation, Gene Expression, Succinate Dehydrogenase Complex Flavoprotein Subunit A Positive, Induction, Melanoma, Hepatitis B Surface Antibody Positive, Investigative Report, Non, HIV Positive, Not, NOS, Conflict, metastatic melanoma, Succinate Dehydrogenase Complex Iron Sulfur Subunit B Positive, Does, KRAS2 Gene Mutation, HIV positive, 1p/19q Codeletion, Visible Radiations, POSITIVE, RAFB1, Guanine Nucleotide Binding Protein (G Protein), Visible Radiation, Ultraviolet B Radiation, Yes, Drives, histopathology, Paired Domain Gene 8 Gene Rearrangement, Mutated, Nucleic Acid Sequencing, SDH2 Positive, conclusion, Heterogeneity, Exomes, AA387315, Programmed Cell Death 1 Ligand 1 Positive, ERBB2 Gene Mutation, ESR2 Positive, Presence, Hepatitis C RNA Positive, early, Type 1, Gene Mutant Negative, Positive Laboratory Test Result, Paired Box 8 Gene Rearrangement, LCAM Gene Mutation, Oncogenesis, Expressed, Took Place, Patient, spine, ER-Beta Positive, Horka, E-Cadherin Gene Mutation, Base, IPSS-R Risk Category Very Low, Gene Mutation Positive, Fs(3)Horka, HRAS Gene Mutation, inherited genetic, Arc-1 Gene Mutation, Harvey Rat Sarcoma Viral Oncogene Homolog Gene Mutation, AV095280, Sequence Analysis, Total RNA-Seq, N-SAM Gene Mutation, N-SAM Gene Rearrangement, Provided, CD274 Positive, Account, Take Place, BRAF Rearrangement, Allelomorphs, Non-, Tumorigeneses, CDH1 Gene Mutation, KRAS-2 Gene Mutation, NS6, PDL1 Positive, Benign Neoplasm, NS7, Anti-HBs Positive, KIT Positive, c-erbB2 Gene Activation, Anti-HBc Antibody Positive, TERT Promoter Mutation, Malignant, KAL2 Gene Mutation, ECT1 Gene Rearrangement, Financial Account, protrusion, SEQUENCING, Anoctamin-1 Positive, Investigative, FGFR-3 Gene Mutation, Fp Positive, Happen, Fibroblast Growth Factor Receptor 1 Gene Rearrangement, Genetic heterogeneity, OGD Gene Mutation, Gene Variant Negative, Anti-HBcAb Positive, DOUBLE IMMUNODIFFUSION, Clinical Progression, Anti-Hepatitis B Virus Surface Antibody Positive, Whole Transcriptome Shotgun Sequencing, Hep C RNA Positive, DmF2, HIV test positive, CD274 Antigen Positive, Current, Epithelial Gene Mutation, MET Proto-Oncogene, lod, Somatic, Erb-B2 Receptor Tyrosine Kinase Gene Mutation, BFGFR Gene Rearrangement, FOCUS, PRESENT, Malignancy, Occur, clinical information, SWS Gene Mutation, TAOS2 Positive, Fibroblast Growth Factor Receptor 3 Gene Mutation, Challenge, Ouchterlony Double Immunodiffusion, Cadherin 1, E-Cadherin (Epithelial) Gene Mutation, HER2/neu Gene Mutation, Visible, BRCA1 Associated Protein 1 Gene Mutation, v-Kit Hardy-Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog Positive, Methylguanine-DNA Methyltransferase Gene Promoter Methylation, Allelomorph, Neuroblastoma RAS Viral Oncogene Homolog Gene Mutation, H-ras Gene Mutation, ETV Gene Rearrangement, Positive Lymph Node, Happened, RNA Sequence Analyses, Found, Clients, heterogeneity, CD332 Gene Rearrangement, C-H-RAS Gene Mutation, Gene Mutant Positive, Ets Variant Gene Family Rearrangement, Intratumoral, RNA Sequencing, HER2 Gene Amplification, OGD Gene Rearrangement, Gene Mutation Not Detected, Known, KAL2 Gene Rearrangement, SDH1 Positive, CTNNB Gene Mutation, progesterone receptor positive, RASH1 Gene Mutation, ER Alpha Positive, UCHL2 Gene Mutation, RAD54L Gene Mutation, Deidentification, EVENTS, Molecular Biology, GNA-11 Gene Mutation, Disease, CEK Gene Rearrangement, Anti-Hepatitis B Virus Core Antibody Positive, malignant, Historical Aspects, Tumorigenesis, Loss of Chromosomes 1p/19q, Historical Aspect, ESTRR Positive, Client, K-SAM Gene Rearrangement, development, Melanomas, del(1p/19q), NR3A2 Positive, Fibroblast Growth Factor Receptor 3 Gene Rearrangement, MGMT Gene Promoter Methylation, CMNS, B-raf, OCCUR, TMEM16A Positive, ESRA Positive, Catenin Beta-1 Gene Mutation, MGMT Methylation, AR Positive, Performed, ERBB2 Mutation, Radiations, Basic, ETV Family Rearrangement, FMS-Like Tyrosine Kinase 2 Gene Mutation, Beta-Catenin Gene Mutation, GA11 Gene Mutation, HIV Positivity, Mast/Stem Cell Growth Factor Receptor Kit Positive, Paired Box Gene 8 Gene Rearrangement, TP2 Promoter Mutation, Photoradiation, Basis, ORAOV2 Positive, FGFR-2 Gene Mutation, patient, arc degree, Calcium-Dependent Adhesion Protein, NUCLEIC ACID SEQUENCING, LTg, Gene Variation Positive, BAP1 Mutation, c-K-ras Gene Mutation, Cancer Progression, Only, Braf-2, RNA Sequence Analysis, FGFR-1 Gene Mutation, malignant melanoma, HBs Antigen Positive, CD274 Molecule Positive, Single, Aspects, Summary, growth, Mitochondrial Positive, Revised International Prognostic Scoring System for Myelodysplastic Syndrome Very Low Risk Category, Field Report, Historical, GTPase Gene MutationfalseMultiregion Whole-Exome Sequencing Uncovers the Genetic Evolution and Mutational Heterogeneity of Early-Stage Metastatic Melanoma.Cancer genome sequencing has shed light on the underlying genetic aberrations that drive tumorigenesis. However, current sequencing-based strategies, which focus on a single tumor biopsy, fail to take into account intratumoral heterogeneity. To address this challenge and elucidate the evolutionary history of melanoma, we performed whole-exome and transcriptome sequencing of 41 multiple melanoma biopsies from eight individual tumors. This approach revealed heterogeneous somatic mutations in the range of 3%-38% in individual tumors. Known mutations in melanoma drivers BRAF and NRAS were always ubiquitous events. Using RNA sequencing, we found that the majority of mutations were not expressed or were expressed at very low levels, and preferential expression of a particular mutated allele did not occur frequently. In addition, we found that the proportion of ultraviolet B (UVB) radiation-induced C>T transitions differed significantly (P < 0.001) between early and late mutation acquisition, suggesting that different mutational processes operate during the evolution of metastatic melanoma. Finally, clinical history reports revealed that patients harboring a high degree of mutational heterogeneity were associated with more aggressive disease progression. In conclusion, our multiregion tumor-sequencing approach highlights the genetic evolution and non-UVB mutational signatures associated with melanoma development and progression, and may provide a more comprehensive perspective of patient outcome. Cancer Res; 76(16); 4765-74.2022-01-27 14:47:30EGAS000010043209606EGAD00001008149EGAC00001002322