{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"technology_type":["Illumina HiSeq 2500"],"study_type":["Other"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001001846"],"host":["EGA"],"description":["EGA study EGAS00001001846"],"dataset_title":["Exome","Transcriptome"],"category":["restricted"],"repository":["EGA"],"name_synonyms":["Therapy, Antemortem Diagnoses, screening, Genomics, Antemortem Diagnosis, findings, Malignant Neoplasm, Comparative, Neoplasms, Benign Neoplasm, histology, Functional Genomics, Tumor, Pdcd1l1, A530045L16Rik, Diagnosis, Malignant, Examination and Diagnoses, Diagnoses, B7h1, morphology, Structural, Postmortem, Screenings, MT, Benign, PDCD1LG1, PDCD1L1, Mass Screenings, Examinations and Diagnoses, Functional, Mass, symptoms, Neoplasm, Screening, Antemortem, Postmortem Diagnosis, anatomy and histology, B7H1, Diagnoses and Examination, treatment, Postmortem Diagnoses, anatomy, primary cancer, B7-H., histopathology, Malignancy, Comparative Genomics, signs, Benign Neoplasms, Cancers, Diagnoses and Examinations, PD-L1, Treatments, malignant tumor, Malignant Neoplasms, Neoplasias, Therapeutic, malignant neoplasm, Pdcd1lg1, disease management, Therapies, Structural Genomics, Treatment, Malignancies, Neoplasia, PDL1, Pdl1, Diagnose, Cancer, Tumors"],"description_synonyms":["AI504024, triple-receptor negative breast cancer, MK-3475, lambrolizumab, Antemortem Diagnosis, short stature, determination, SOFT, Breast Neoplasms, Gene Expression Profile, histology, jal, Progress Reports, Profiles, Tumor, xgata-3, JTK10, Diagnosis, HDRS, TNBC, Tp53, soft, Mutations, triple-negative breast cancer, Personal, ras, PDCD1L1, Summary Report, bbl, triple-negative breast carcinoma, symptoms, cytopathology, tumour of soft tissue and skeleton, C-K-RAS, B7-H1, anatomy and histology, Summary Reports, k-ras, Non Polyadenylated, Decision-Making, rask2, Psychological, treatment, Programmed death ligand 1, Progress Report, BCC7, Triple Negative Breast Cancer, Genomes, GATA-3, Breast Cancers, C1, Polyadenylated Messenger, Tissue, Medical Decision-Making, chromatid, Signatures, high grade, Social, Progress, Sarcoma, Field Reports, malignant neoplasm, Expression Signature, disease management, Therapies, Transcriptomes, onychodysplasia, Malignancies, stage, Social Power, Gata-3, PDL1, Pdl1, connective and soft tissue neoplasm, Diagnose, Power, Tumors, Therapy, screening, Polyadenylated, Ki-ras, Expression Profiles, Triple-Negative Breast Cancer, Psychological Powers, A530045L16Rik, JAK2, results, Diagnoses, Programs, Gene Expression, THCYT3, Benign, Postmortem, Screenings, JAK-2, Investigative Report, Clinical Decision Making, PDCD1LG1, Expression Signatures, Examinations and Diagnoses, p21, B7-H, Chemotherapy, Triple-Negative, simple tissue, bfy, PIX2, Postmortem Diagnosis, Expression Profile, region, Transcriptome Profiles, Polyadenylated Messenger RNA, Diagnoses and Examination, B7 homolog 1, Postmortem Diagnoses, XGATA3, Triple-Negative Breast Neoplasms, B7-H., Non Polyadenylated mRNA, Spindle Cell, histopathology, Pharmacotherapy, protein_coding_transcript, ER Negative PR Negative HER2 Negative Breast Cancer, ER-Negative PR-Negative HER2-Negative Breast Neoplasms, Field, Exomes, signs, Benign Neoplasms, HDR, whole genome, sarcoma of the soft tissue and bone, Treatments, Non-Polyadenylated mRNA, Malignant Neoplasms, Atlases, Phenotypes, Report, Patient, sarcoma of soft tissue and bone, RASK2, Chromosome, antagonists and inhibitors, Epithelioid Sarcoma, Triple-Negative Breast Neoplasm, facial dysmorphism, P53, p44, bhy, other neoplasm, Powers, ER-Negative PR-Negative HER2-Negative Breast Cancer, Poly(A) RNA, Soft Tissue, KI-RAS, Psychological Power, whole exome, localised, Transcriptome Profile, Professional Power, chemotherapy, Neoplasms, developmental stage, Kras2, NS3, p53, Spindle Cell Sarcomas, Benign Neoplasm, Triple-Negative Breast Cancers, Gene, pharmacotherapy, Janus kinase 2, Pharmacotherapies, Malignant, LFS1, Chemotherapies, and hypotrichosis, morphology, Investigative, Soft Tissue Sarcoma, Messenger, Mass, Kras-2, Screening, C81284, Antemortem, Medical, Drug Therapies, KRAS2, KRAS1, p21B, CD274, Sarcomas, anatomy, Clinical, Malignancy, Profile, K-RAS4B, K-RAS4A, inhibiteur, messenger RNA, tumor of soft tissue and skeleton, PD-L1, Diagnoses and Examinations, Neoplasias, template RNA, Trp53, inhibidor, SCH-900475, Clients, Triple Negative Breast Neoplasm, Medical Decision Making, site, Keytruda, TRP53, Spindle Cell Sarcoma, Investigative Reports, Cancer, disease remission, inhibitors, Antemortem Diagnoses, sarcoma, RNA, Transcriptome, findings, Malignant Neoplasm, malignant, K-RAS2B, K-RAS2A, Messenger RNA, inhibitor, K-ras, c-Ki-ras, Pdcd1l1, Client, Examination and Diagnoses, Xp53, B7h1, prophase chromosome, Fd17, MT, Mass Screenings, Epithelioid Sarcomas, Poly(A)+ mRNA, Research Reports, Gene Expression Signatures, chemical analysis, Neoplasm, INSDC_feature:mRNA, PDCD1 ligand 1, focal, Professional, Gene Expression Signature, Polyadenylated RNA, AI929937, WDR51A, Epithelioid, B7H1, antagonists, primary cancer, NS, Breast Neoplasm, Poly(A)+ RNA, mRNA, Poly(A) Tail, interphase chromosome, Non-Polyadenylated, Soft Tissue Sarcomas, Cancers, malignant tumor, Drug, ER Negative PR Negative HER2 Negative Breast Neoplasms, Personal Power, Therapeutic, Reports, DEL, Gene Expression Profiles, kras, Pdcd1lg1, mesenchymal tumor, CFC2, Breast Cancer, Power (Psychology), Treatment, pharmacologic therapy, assay, Signature, biopsy, Summary, Polyadenylated mRNA, Neoplasia, Field Report"],"additional_accession":[]},"is_claimable":false,"name":"Integration of genomics and histology reveals diagnosis and effective therapy of refractory cancer of unknown primary with PDL1 amplification (H021)","description":"Identification of the tissue of origin in cancer of unknown primary (CUP) poses a diagnostic challenge and is critical for directing site-specific therapy. Currently, clinical decision making in patients with CUP primarily relies on histopathology and clinical features. Comprehensive molecular profiling has the potential to contribute to diagnostic categorization and, most importantly, guide CUP therapy through identification of actionable lesions. We here report the case of an advanced-stage malignancy initially mimicking poorly differentiated soft-tissue sarcoma that did not respond to multi-agent chemotherapy. Molecular profiling within a clinical whole-exome and transcriptome sequencing program revealed a heterozygous, highly amplified KRAS G12S mutation, compound-heterozygous TP53 mutation/deletion, high mutational load, and focal amplification of chromosomes 9p (including PDL1 [CD274] and JAK2) and 10p (including GATA3). Integrated analysis of molecular data and conventional histopathology suggested a diagnosis of triple-negative breast cancer (TNBC) and provided a rationale for immune checkpoint inhibitor therapy with pembrolizumab, which resulted in rapid clinical improvement and a lasting partial remission. Analysis of 157 TNBC samples from The Cancer Genome Atlas revealed focal, high-level PDL1 amplification coinciding with excessive PDL1 mRNA expression in 24% of cases. Collectively, these results illustrate the diagnostic utility of multidimensional tumor profiling in cases with non-descript histology and immune phenotype, demonstrate the predictive power of genomic PDL1 amplification for immune checkpoint inhibition, and suggest a targeted therapeutic strategy in chromosome 9p24.1/PDL1-amplified cancers.H021","dates":{"updated":"2017-07-26 15:39:27"},"accession":"EGAS00001001846","cross_references":{"TAXONOMY":["9606"],"EGA":["EGAD00001002162","EGAD00001002163","EGAC00001000452"]}}