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http://purl.uniprot.org/citations/32816945http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/32816945http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

To determine if a targeted exome panel utilizing matched normal DNA can accurately detect germline and somatic HLA genes in patients with synovial sarcoma (SS) and whether select HLA-A*02 genotypes are prognostic or predictive of outcome in metastatic SS.

Experimental design

Patients with metastatic SS consented to HLA typing by a Clinical Laboratory Improvement Amendments (CLIA)-certified test to determine eligibility for a clinical trial of NY-ESO-1-specific engineered T cells restricted to carriers of HLA-A*02:01, -A*02:05, or -A*02:06 (HLA-A*02 eligible). HLA genotype was determined from Memorial Sloan Kettering Integrated Molecular Profiling of Actionable Cancer Targets (MSK-IMPACT), where feasible, and somatic loss of heterozygosity (LOH) in HLA alleles was identified. Overall survival (OS) was estimated and stratified by HLA-A*02 eligibility.

Results

A total of 23 patients had HLA genotyping by a CLIA-certified lab and MSK-IMPACT. Ninety percent (108/110) of the sequenced alleles were concordant between IMPACT and the outside lab. LOH of HLA genes was detected in three tumors, one had loss of HLA-A*02:01. In total, 66 patients were screened for T-cell therapy and 20 (30%) were HLA-A*02 eligible on outside testing. Univariate analysis of OS from the time of metastasis found HLA-A*02 eligibility was marginally associated with shorter OS [HR = 1.95; 95% confidence interval (CI), 0.995-3.813; P = 0.052]. On multivariate analysis, older age and larger tumor size, but not HLA-A*02 eligibility, were significantly associated with decreased OS. HLA-A*02 eligibility did not impact OS after chemotherapy or pazopanib in the metastatic setting.

Conclusions

Targeted gene panels like MSK-IMPACT may accurately report HLA type and identify loss of somatic HLA alleles. In a multivariable model, HLA-A*02 eligibility was not significantly associated with OS in patients with metastatic SS."xsd:string
http://purl.uniprot.org/citations/32816945http://purl.org/dc/terms/identifier"doi:10.1158/1078-0432.ccr-20-0832"xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/author"Dickson M."xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/author"Kelly C."xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/author"Donoghue M."xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/author"Qin L.X."xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/author"Antonescu C.R."xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/author"Chi P."xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/author"Rosenbaum E."xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/author"Gounder M."xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/author"Movva S."xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/author"Tap W.D."xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/author"D'Angelo S.P."xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/author"Bandlamudi C."xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/author"Keohan M.L."xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/author"Slotkin E.K."xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/author"Nacev B."xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/author"Seier K."xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/author"Simeone N."xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/date"2020"xsd:gYear
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/name"Clin Cancer Res"xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/pages"5448-5455"xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/title"HLA Genotyping in Synovial Sarcoma: Identifying HLA-A*02 and Its Association with Clinical Outcome."xsd:string
http://purl.uniprot.org/citations/32816945http://purl.uniprot.org/core/volume"26"xsd:string
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