EGAGenomicsOtherhttps://ega-archive.org/studies/EGAS00001007661EGAEGA study EGAS00001007661Targeted and shallow whole genome sequencing identifies therapeutic opportunities in p53abn endometrial cancersEGArestrictedTherapy, Complete, Whole Genome, Malignant Neoplasm, Malignancy, Neoplasms, Complete Genome Sequencing, Benign Neoplasm, Genome Sequencing, Benign Neoplasms, Cancers, Tumor, Malignant, Treatments, Sequencing, Neoplasias, low depth, Complete Genome, MT, Benign, Therapeutic, Whole, Therapies, Neoplasm, Treatment, Malignancies, shallow, Neoplasia, Cancer, Tumors, Malignant Neoplasms.l(1)d norm-12, Experimental Designs, Erbb-2, PP2A[[C]], Formol, PR53, PR55, EG:17A9.1, Adjustments, BR_C, l(3)S026326, Laboratory, Design, Error Sources, mental retardation, PP2A[B], 2Bc, pr53, anon-WO0118547.420, MYC, Myc, mixed Mullerian tumour, Tumor, PP2A-Aalpha, B430311C09Rik, Mutations, p110-alpha, DmelCG7109, low depth, B', Kiaa3023, l(1)2Bad, Immunogold-Silver Techniques, l(3)S031807, l(1)2Bab, EG:BACN5I9.1, Method, PP2A 28D, Associations, br-Z1, Methanal, Parafilm, br-Z3, IRIS, CycE1, PP2A[C], myc, Research Activity, l(3)01436, l(1)dn1, Laboratory Research, l(3)S110815, Priorities, treatment, rbp, medium tumor antigen-associated 61 kDa protein, hypoparathyroidism with short stature, Pp2A, PP2a, l(3)S026226, Homologous, dm/dMyc, l(3)S027313, Matched Group, BR, Oxomethane, l(3)S141309, Matched, PNCA4, aar, associated with Dysmorphism, pp2a, FBW6, FBW7, Br-C-Z3, l(3)02414, Fbw7, MCAP, DmelCG6235, PR65, l(3)S035505b, Immunogold-Silver Technic, PP2A, Reporting, CDC4, Cdc4, Immunolabeling Technique, l(3)S048006, Br, BRC-Z2, BRC-Z3, BRC-Z1, Pp2A-28D, l(3)S048013, BRC-Z4, shallow, HRD, PP2A[A], Data Reporting, Tumors, rdp, rds, hereditary breast ovarian cancer, l(3)S067915, dmyc1, Research Technic, Research Methodology, DP, l(1)d.norm.1, CG7901, Immunogold Technique, Research Priorities, pp2aaalpha, MLN19, l(1)npr-1, l(3)S091905, l(1)npr1, Research Proposal, PP2-AB, serine/threonine protein phosphatase 2A, Fbwd6, Experimental, Benign, Immunolabeling Technic, Dm, PR65A, 1466/06, Immunolabeling Technics, DmPp2A-28D, l(3)S029403, Technics, Problem Formulation, l(3)S033903, mMyc, c-neu, CG7913, Research and Development, Wrd, AW538188, l(3)S042630, Benign Neoplasms, pp2A-B', Immunogold Silver Techniques, whole genome, D-Myc, Malignant Neoplasms, Formulations, Activities, dPP2A A, l(3)S075902b, wrd, A/PR65, AGO, l(3)S066813, l(3)S027127, associated with dysmorphism, l(1)pp-2, B56-2, l(1)pp-1, dMyc1, l(3)S042629, Data Adjustments, B56-1, RNF53, CG10798, l(3)S063110, Immunogold-Silver, SEL-10, hCdc4, LD02456, dm/myc, dPP2A-B56-1, Neoplasms, dPP2A-B56-2, Matched Groups, number, CG5643, dMyc, dMYC, l(3)S132907, CG11511, FBXW6, Adjustment, CG11514, cyclinE, l(3)S069206a, l(3)S023141a, Sources, Nop30, bHLHe57, CG17291, HER-2/neu, i234, Technique, Immunogold Silver Technics, l(3)S119908, l(3)j11C8, l(3)S046918, Complete, Whole Genome, PP2A[B'-1], l(3)S088513, dPP2A-Balpha, Complete Genome Sequencing, Dmyc, DMYc, dPP2A-C, FANCS, ppp2r1a, 5559, Sequencing, and seizures, BEST:LD02456, Research Strategy, Neoplasias, PP2A[B'-2], DPR65, Formalin, Nird, RNCMYC, l(3)S029110, Whole, FBXO30, l(1)PP1, l(1)pp1, Development and Research, MCM, l(1)pp2, Carcinosarcomas, PP2Ac, bHLHe39, ppp2r2c, dmyc, PP2Aa, Cancer, Neu, NEU, l(3)S076415, FBX30, EG:123F11.1, l(3)S023938, DPR55, CG 7913, Malignant Neoplasm, Immunogold Technic, EP3559, HER-2|neu, Immunohistocytochemistry, PSCP, l(1)G0284a, Research Strategies, MT, DmelCG5643, CWS5, hypoparathyroidism, Neoplasm, PP2A C, NGL, PP2A A, KCS1, Immunolabeling, PP2AAALPHA, l(2)02496, Immunocytochemistry, DmelCG17291, c-erbB2, l(2)s5286, l(3)S032303, pac2, Research Designs, l(3)S075110, Cancers, Research Technics, pp2a-aalpha, tws/aar, l(3)S105605, growth retardation and developmental delay, Data Adjustment, caPI3K, CLOVE, Error, Oxomethylene, ppp2r2b-a, l(1)G0401, Immunogold-Silver Technics, Immunolabeling Techniques, BRC, Strategy, KCS, Neoplasia, Pp2A29B, chromosomal crossover, Research Technique, Problem Formulations, mixed tumor, l(3)S025913, CCNE, Activity, DmelCG7913, Feature, myc-B, PI3K, DmelCG10798, PPP2R1A, l(3)S060804, BR-C, Technic, PPP1R53, pr65a, CD340, l(3)S024838, l(3)S025806, Recombinations, Techniques, c-MYC, c-Myc, l(3)S045519, A18, br-C, Ccne, l(3)S043008b, congenital, Immunogold-Silver Technique, PP1, Familiar breast and Ovarian cancer syndrome, Tws, ARC, 0318/07, PP2, p110alpha, l(3)S031006, l(3)S053011, BROVCA1, l(3)S080409, BR-c, Br-C, ccne, Experimental Design, Br-Z4, Group, c-myc, l(3)s1801, l(1)G0318, BRCC1, l(3)S049902, de12, l(3)S067109b, cycE3, TYPE 2A SERINE/THREONINE PROTEIN PHOSPHATASE, Formaldehyd, l(1)n34, Designs, BrC-Z1, Groups, MTS/PP2A, experimental design, v158, R75353, disease management, Therapies, Research Techniques, F20P5.30, Fbx30, Malignancies, Research Priority, MCMTC, CG11491, Immunogold Technics, ER2-6, l(3)S043029, F20P5_30, Therapy, l(3)S024834a, tw, PP2a 28D, AU016757, BRCA1, l(3)S025832, BRCA2, l(3)S022440, BR-C Z1, CG7109, Genome Sequencing, Research Proposals, BRCAI, B/PR55, l(3)S101413b, Pp2A-85F, uq, results, l(3)S023309, Immunogold, Immunogold Techniques, Complete Genome, l(3)S110008a, and developmental delay, NOP, Fbxw6, nrp1, Problem, fixed, BcDNA:LD34343, l(3)S029701a, l(1)G0354, ptpa, Recombination, PP2A B', l(1)G0359, PTPA, CG6235, common, npr-1, l(3)S061915, d-myc, Features, Treatments, CG33297, Myc2, l(3)S066017, MLN 19, l(3)S032708c, Niard, l(3)S023206, myc2, Patient, l(3)S134601a, npr, TKR1, l(3)S022361, l(3)S061805, MRTL, 1110001A17Rik, l(1)G0018, DmelCG11491, l(1)G0139, Benign Neoplasm, PP2A-29B, l(1)ts144, Wdb, l(1)2Ba, dPP2A, l(1)2Bb, Scoring Method, Z1, l(1)2Bc, Z2, Z3, l(3)S075515b, Z4, l(3)S111515, Malignant, Fbw7-gamma, presence, CG13383, CYCLE, dPR55, anon-WO03040301.171, l(3)S048507, EG:25D2.1, MYCC, RRG6, Scoring Methods, nrp, Br-C Z2, l(1)ts132, c-myc II, l(1)ts376, dB56-2, dB56-1, intellectual disability, BcDNA:GM05554, l(1)ESHS5, PP2A-A, B'/PR61, Methodology, rdp., PP2A-B, l(3)S022205b, PP2A-C, Scoring, Malignancy, l(3)S146606, Research, Proposals, HER-2, Growth retardation, nprl, Fbxo30, BHLHE39, PP2A subunit A isoform R1-alpha, l(1)G0042, l(1)G0284, GEP6, l(1)2Bd, SEL10, Clients, l(3)S024455, Error Source, Fbw7-alpha, npr1, Characteristics, Strategies, 6330412C24Rik, l(3)S060203, Homologous Recombinations, Mts, l(3)S023013, mKIAA3023, p110, ecs, BrZ3, Formulation, l(3)S028707, Client, l(3)S052810, count in organism, mixed Mullerian tumor, Priority, Characteristic, o.c.c., Research Activities, hAgo, FORMALIN, Proposal, Methods, distinct, l(1)ts358, Source, reciprocal DNA recombination, PP2A subunit A isoform PR65-alpha, Methylene oxide, 2B5, Therapeutic, Data, cardinality, Mullerian, 2414, Treatment, 6330556D22Rik, HER2falseTargeted and shallow whole genome sequencing identifies therapeutic opportunities in p53abn endometrial cancersPurpose: Shallow whole genome sequencing (sWGS) can detect copy number (CN) aberrations. In high-grade serous ovarian (HGSOC) sWGS identified CN signatures such as homologous recombination deficiency (HRD) to direct therapy. We applied sWGS with targeted sequencing to p53abn endometrial cancers (ECs) to identify additional prognostic stratification and therapeutic opportunities. Experimental Design: sWGS and targeted panel sequencing was performed on formalin-fixed paraffin-embedded p53abn ECs. CN alterations, mutational data and CN signatures were derived, and associations to clinicopathologic and outcomes data were assessed. Results: In 187 p53abn ECs, 5 distinct CN signatures were identified. Signature 5 was associated with BRCA1/2 CN loss with features similar to HGSOC HRD signature. 22% potential HRD cases were identified, 35 patients with signature 5, and 8 patients with BRCA1/2 somatic mutations. Signatures 3 and 4 were associated with whole genome duplication, and CCNE1, ERBB2 and MYC amplifications, with mutations in PIK3CA enriched in signature 3. We observed improved overall survival (OS) for patients with signature 2 and worse OS for signatures 1 and 3. 28% of patients had CCNE1 amplification and this subset was enriched with carcinosarcoma histotype. 34% of patients, across all histotypes, had ERBB2 amplification and/or HER2 overexpression on immunohistochemistry, which was associated with worse outcomes. Mutations in PPP2R1A (29%) and FBXW7 (16%) were among the top 5 most common mutations. Conclusions: sWGS and targeted sequencing identified therapeutic opportunities in 75% of p53abn EC patients. Further research is needed to determine the efficacy of treatments targeting these identified pathways within p53abn ECs.2024-04-17 12:10:56EGAS000010076619606EGAD00001015241EGAD00001015349EGAC00000000011