Abstract 1982: Development of reference material for blood tumor mutational burden measurement
| Autor: | Omoshile Clement, Andrew Anfora, Bharathi Anekella, Russell Garlick, Dan Brudzewsky, Yves Konigshofer, Matthew G. Butler |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Cancer Research. 80:1982-1982 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2020-1982 |
| Popis: | Tumor mutational burden (TMB) is a measurement of the somatic mutations acquired by a tumor genome that cause nonsynonymous changes in proteins. TMB is a biomarker that serves as a proxy for the potential to produce neoantigens that will be recognized by T cells. Despite some reports to the contrary, TMB has successfully categorized the likelihood that an individual will respond positively to immune checkpoint inhibitors in some clinical trials. Although most TMB measurements are made from genomic DNA extracted from formalin-fixed and paraffin-embedded tissue sections, some diagnostic tests measure TMB in circulating tumor DNA (ctDNA) extracted from blood samples; an approach referred to as blood TMB (bTMB). Blood TMB is an attractive biomarker since it bypasses many of the obstacles encountered with resected and hard to biopsy tumors. Only a handful of diagnostic laboratories measure bTMB and their analytic validations rely on hard to obtain specimens acquired from ongoing drug trials or tissue repositories. This specimen scarcity impedes in depth analytic assay validation and the generation of harmonized bTMB data. For bTMB measurements to become routine, robust, and accessible to all diagnostic laboratories, we developed contrived patient-like bTMB reference materials. Blood TMB reference materials were formulated by blending and sizing genomic DNA purified from tumor and corresponding normal cell lines by proprietary methodology. Fragment analysis demonstrated that the bTMB reference materials mimic the size distribution typical of purified ctDNA. Sequencing by a targeted gene panel showed the bTMB reference materials had variant allele frequencies (VAFs) characteristic of ctDNA. For example, bTMB reference materials produced with either 2.0 or 0.5% tumor content had mean VAFs of approximately 1.0 and 0.3 %, respectively. Additional sequencing of bTMB reference materials by other gene panels demonstrated comparable results. Evaluation of contrived bTMB reference materials with various cancer gene panels will assist in the standardization of the measurement of bTMB, an emerging biomarker for clinical utility of immune checkpoint inhibitor therapy. Citation Format: Matthew G. Butler, Yves Konigshofer, Omoshile Clement, Andrew Anfora, Dan Brudzewsky, Bharathi Anekella, Russell Garlick. Development of reference material for blood tumor mutational burden measurement [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1982. |
| Databáze: | OpenAIRE |
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