POLE proofreading mutation, immune response and prognosis in endometrial cancer
نویسندگان
چکیده
Endometrial cancers (ECs) with POLE proofreading mutations are typified by ultramutation and excellent prognosis. We investigated whether these were related, and found that POLE-mutant ECs display a robust T cell response that corresponds to an enrichment of antigenic tumor neopeptides. Enhanced immunogenicity may explain the favorable outcome of POLE-mutant ECs.
منابع مشابه
Biology of Human Tumors POLE Proofreading Mutations Elicit an Antitumor Immune Response in Endometrial Cancer
Purpose: Recent studies have shown that 7% to 12% of endometrial cancers are ultramutated due to somatic mutation in the proofreading exonuclease domain of the DNA replicase POLE. Interestingly, these tumors have an excellent prognosis. In view of the emerging data linking mutation burden, immune response, and clinical outcome in cancer, we investigatedwhether POLE-mutant endometrial cancers sh...
متن کاملPOLE Proofreading Mutations Elicit an Antitumor Immune Response in Endometrial Cancer.
PURPOSE Recent studies have shown that 7% to 12% of endometrial cancers are ultramutated due to somatic mutation in the proofreading exonuclease domain of the DNA replicase POLE. Interestingly, these tumors have an excellent prognosis. In view of the emerging data linking mutation burden, immune response, and clinical outcome in cancer, we investigated whether POLE-mutant endometrial cancers sh...
متن کاملPOLE proofreading mutations elicit an anti-tumor immune response in endometrial cancer Running title: POLE mutations and immune response in endometrial cancer Authors:
Affiliations: 1 Department of Pathology, Leiden University Medical Center, Albinusdreef 2, Postbus 9600, 2300 RC Leiden, The Netherlands 2 University of Groningen, University Medical Center Groningen, Department of Obstetrics and Gynecology, PO 30.001 9700 RB Groningen, The Netherlands 3 Molecular and Population Genetics Laboratory, The Wellcome Trust Centre for Human Genetics, University of Ox...
متن کاملPrognostic Significance of POLE Proofreading Mutations in Endometrial Cancer
BACKGROUND Current risk stratification in endometrial cancer (EC) results in frequent over- and underuse of adjuvant therapy, and may be improved by novel biomarkers. We examined whether POLE proofreading mutations, recently reported in about 7% of ECs, predict prognosis. METHODS We performed targeted POLE sequencing in ECs from the PORTEC-1 and -2 trials (n = 788), and analyzed clinical outc...
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Accurate duplication of DNA prior to cell division is essential to suppress mutagenesis and tumour development. The high fidelity of eukaryotic DNA replication is due to a combination of accurate incorporation of nucleotides into the nascent DNA strand by DNA polymerases, the recognition and removal of mispaired nucleotides (proofreading) by the exonuclease activity of DNA polymerases δ and ε, ...
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