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@article{1744844,
author = {Pálová, Hana and Kýr, Michal and Pál, Karol and Merta, Tomáš and Múdry, Peter and Polášková, Kristýna and Catela Ivković, Tina and Adamcová, Soňa and Hornakova, Tekla and Ježová, Marta and Křen, Leoš and Štěrba, Jaroslav and Slabý, Ondřej},
article_location = {BASEL},
article_number = {1},
doi = {http://dx.doi.org/10.3390/cancers12010230},
keywords = {pediatric tumors; tumor mutational burden; TMB; whole-exome sequencing; gene panel sequencing; immune checkpoint inhibitors},
language = {eng},
issn = {2072-6694},
journal = {Cancers},
title = {Assessment of Tumor Mutational Burden in Pediatric Tumors by Real-Life Whole-Exome Sequencing and In Silico Simulation of Targeted Gene Panels: How the Choice of Method Could Affect the Clinical Decision?},
url = {https://www.mdpi.com/2072-6694/12/1/230},
volume = {12},
year = {2020}
}
TY - JOUR
ID - 1744844
AU - Pálová, Hana - Kýr, Michal - Pál, Karol - Merta, Tomáš - Múdry, Peter - Polášková, Kristýna - Catela Ivković, Tina - Adamcová, Soňa - Hornakova, Tekla - Ježová, Marta - Křen, Leoš - Štěrba, Jaroslav - Slabý, Ondřej
PY - 2020
TI - Assessment of Tumor Mutational Burden in Pediatric Tumors by Real-Life Whole-Exome Sequencing and In Silico Simulation of Targeted Gene Panels: How the Choice of Method Could Affect the Clinical Decision?
JF - Cancers
VL - 12
IS - 1
SP - 1-14
EP - 1-14
PB - MDPI
SN - 20726694
KW - pediatric tumors
KW - tumor mutational burden
KW - TMB
KW - whole-exome sequencing
KW - gene panel sequencing
KW - immune checkpoint inhibitors
UR - https://www.mdpi.com/2072-6694/12/1/230
N2 - Background: Tumor mutational burden (TMB) is an emerging genomic biomarker in cancer that has been associated with improved response to immune checkpoint inhibitors (ICIs) in adult cancers. It was described that variability in TMB assessment is introduced by different laboratory techniques and various settings of bioinformatic pipelines. In pediatric oncology, no study has been published describing this variability so far. Methods: In our study, we performed whole exome sequencing (WES, both germline and somatic) and calculated TMB in 106 patients with high-risk/recurrent pediatric solid tumors of 28 distinct cancer types. Subsequently, we used WES data for TMB calculation using an in silico approach simulating two The Food and Drug Administration (FDA)-approved/authorized comprehensive genomic panels for cancer. Results: We describe a strong correlation between WES-based and panel-based TMBs; however, we show that this high correlation is significantly affected by inclusion of only a few hypermutated cases. In the series of nine cases, we determined TMB in two sequentially collected tumor tissue specimens and observed an increase in TMB along with tumor progression. Furthermore, we evaluated the extent to which potential ICI indication could be affected by variability in techniques and bioinformatic pipelines used for TMB assessment. We confirmed that this technological variability could significantly affect ICI indication in pediatric cancer patients; however, this significance decreases with the increasing cut-off values. Conclusions: For the first time in pediatric oncology, we assessed the reliability of TMB estimation across multiple pediatric cancer types using real-life WES and in silico analysis of two major targeted gene panels and confirmed a significant technological variability to be introduced by different laboratory techniques and various settings of bioinformatic pipelines.
ER -
PÁLOVÁ, Hana, Michal KÝR, Karol PÁL, Tomáš MERTA, Peter MÚDRY, Kristýna POLÁŠKOVÁ, Tina CATELA IVKOVI$\backslash$'C, Soňa ADAMCOVÁ, Tekla HORNAKOVA, Marta JEŽOVÁ, Leoš KŘEN, Jaroslav ŠTĚRBA and Ondřej SLABÝ. Assessment of Tumor Mutational Burden in Pediatric Tumors by Real-Life Whole-Exome Sequencing and In Silico Simulation of Targeted Gene Panels: How the Choice of Method Could Affect the Clinical Decision? \textit{Cancers}. BASEL: MDPI, 2020, vol.~12, No~1, p.~1-14. ISSN~2072-6694. Available from: https://dx.doi.org/10.3390/cancers12010230.
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