Multicentric pilot study to standardize clinical whole exome sequencing (WES) for cancer patients

被引：17

作者：

Menzel, Michael ^{[1
,2
]}

Ossowski, Stephan ^{[3
,4
,5
]}

Kral, Sebastian ^{[6
,7
]}

Metzger, Patrick ^{[7
,8
]}

Horak, Peter ^{[2
,9
,10
]}

Marienfeld, Ralf ^{[11
,12
]}

Boerries, Melanie ^{[7
,8
,13
,14
]}

Wolter, Steffen ^{[6
,7
]}

Ball, Markus ^{[1
,2
]}

Neumann, Olaf ^{[1
,2
]}

Armeanu-Ebinger, Sorin ^{[3
,4
]}

Schroeder, Christopher ^{[3
,4
]}

Matysiak, Uta ^{[6
,7
]}

Goldschmid, Hannah ^{[1
,2
]}

Schipperges, Vincent ^{[7
,8
]}

Fuerstberger, Axel ^{[11
,12
,15
]}

Allgaeuer, Michael ^{[1
,2
]}

Eberhardt, Timo ^{[11
,12
]}

Niewoehner, Jakob ^{[11
]}

Blaumeiser, Andreas ^{[7
,8
,14
]}

Ploeger, Carolin ^{[1
,2
]}

Haack, Tobias Bernd ^{[3
,4
]}

Tay, Timothy Kwang Yong ^{[1
,2
,16
]}

Kelemen, Olga ^{[3
,4
]}

Pauli, Thomas ^{[7
,8
]}

Kirchner, Martina ^{[1
,2
]}

Kluck, Klaus ^{[1
,2
]}

Ott, Alexander ^{[3
,4
]}

Renner, Marcus ^{[1
,2
,9
]}

Admard, Jakob ^{[3
,4
]}

Gschwind, Axel ^{[3
,4
]}

Lassmann, Silke ^{[6
,7
]}

Kestler, Hans ^{[11
,12
]}

Fend, Falko ^{[17
]}

Illert, Anna Lena ^{[18
,19
,20
]}

Werner, Martin ^{[6
,7
,14
]}

Moeller, Peter ^{[11
]}

Seufferlein, Thomas Theodor Werner ^{[12
,21
]}

Malek, Nisar ^{[4
,22
]}

Schirmacher, Peter ^{[1
,2
,10
]}

Froehling, Stefan ^{[2
,9
,10
]}

Kazdal, Daniel ^{[1
,2
]}

Budczies, Jan ^{[1
,2
,10
]}

Stenzinger, Albrecht ^{[1
,2
,10
]}

机构：

[1] Heidelberg Univ Hosp, Inst Pathol, Heidelberg, Germany

[2] Ctr Personalized Med ZPM, Heidelberg, Germany

[3] Univ Tubingen, Inst Med Genet & Appl Genom, Tubingen, Germany

[4] Ctr Personalized Med ZPM, Tubingen, Germany

[5] Univ Tubingen, Inst Bioinformat & Med Informat IBMI, Tubingen, Germany

[6] Univ Freiburg, Inst Surg Pathol, Med Ctr, Freiburg, Germany

[7] Ctr Personalized Med ZPM, Freiburg, Germany

[8] Univ Freiburg, Freiburg Univ Med Ctr, Inst Med Bioinformat & Syst Med IBSM, Fac Med, Freiburg, Germany

[9] Heidelberg & German Canc Res Ctr DKFZ, Natl Ctr Tumor Dis NCT, Div Translat Med Oncol, D-69120 Heidelberg, Germany

[10] German Canc Consortium DKTK, Heidelberg, Germany

[11] Univ Hosp Ulm, Inst Pathol, Ulm, Germany

[12] Ctr Personalized Med ZPM, Ulm, Germany

[13] Univ Freiburg, Fac Med, Comprehens Canc Ctr Freiburg CCCF, Med Ctr, Freiburg, Germany

[14] German Canc Consortium DKTK, German Canc Res Ctr DKFZ, Partner Site Freiburg, Heidelberg, Germany

[15] Ulm Univ, Inst Med Syst Biol, Ulm, Germany

[16] Singapore Gen Hosp, Dept Anat Pathol, Singapore, Singapore

[17] Univ Hosp Tubingen, Inst Pathol & Neuropathol, Tubingen, Germany

[18] Univ Freiburg, Fac Med, Med Ctr, Dept Radiol,Med Phys, D-79085 Freiburg, Germany

[19] Tech Univ Munich, Klinikum Rechts Isar, Nukl Med Klin & Poliklin, D-81675 Munich, Germany

[20] German Canc Consortium DKTK, Partner Site Munich & German Canc Res Ctr DKFZ, Heidelberg, Germany

[21] Univ Hosp Ulm, Dept Internal Medicine1, Ulm, Germany

[22] Univ Hosp Tubingen, Dept Internal Med, Tubingen, Germany

来源：

NPJ PRECISION ONCOLOGY | 2023年 / 7卷 / 01期

关键词：

COPY NUMBER; PERSONALIZED MEDICINE; TUMOR; GENOMICS; ONCOLOGY;

D O I：

10.1038/s41698-023-00457-x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

A growing number of druggable targets and national initiatives for precision oncology necessitate broad genomic profiling for many cancer patients. Whole exome sequencing (WES) offers unbiased analysis of the entire coding sequence, segmentation-based detection of copy number alterations (CNAs), and accurate determination of complex biomarkers including tumor mutational burden (TMB), homologous recombination repair deficiency (HRD), and microsatellite instability (MSI). To assess the inter-institution variability of clinical WES, we performed a comparative pilot study between German Centers of Personalized Medicine (ZPMs) from five participating institutions. Tumor and matched normal DNA from 30 patients were analyzed using custom sequencing protocols and bioinformatic pipelines. Calling of somatic variants was highly concordant with a positive percentage agreement (PPA) between 91 and 95% and a positive predictive value (PPV) between 82 and 95% compared with a three-institution consensus and full agreement for 16 of 17 druggable targets. Explanations for deviations included low VAF or coverage, differing annotations, and different filter protocols. CNAs showed overall agreement in 76% for the genomic sequence with high wet-lab variability. Complex biomarkers correlated strongly between institutions (HRD: 0.79-1, TMB: 0.97-0.99) and all institutions agreed on microsatellite instability. This study will contribute to the development of quality control frameworks for comprehensive genomic profiling and sheds light onto parameters that require stringent standardization.

引用

页数：11

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