Currently favored sampling practices for tumor sequencing can produce optimal results in the clinical setting

Tumor heterogeneity is a consequence of clonal evolution, resulting in a fractal-like architecture with spatially separated main clones, sub-clones and single-cells. As sequencing an entire tumor is not feasible, we ask the question whether there is an optimal clinical sampling strategy that can han...

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Vydáno v:	Scientific reports Ročník 10; číslo 1; s. 14403
Hlavní autoři:	Pongor, Lőrinc S., Munkácsy, Gyöngyi, Vereczkey, Ildikó, Pete, Imre, Győrffy, Balázs
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 01.09.2020 Nature Publishing Group
Témata:	631/114 631/208 631/67 631/67/68 692/4028 692/4028/67/68 Anaplastic large-cell lymphoma Biopsy Cancer Clonal Evolution - genetics DNA microarrays Exome Female Fibronectin Gene Frequency Genetic Heterogeneity Germ-Line Mutation Heterogeneity High-Throughput Nucleotide Sequencing - methods Humanities and Social Sciences Humans Lymphoma Mesenchyme Metastases multidisciplinary Mutation Mutation Rate Non-coding RNA Ovarian cancer Ovarian Neoplasms - genetics Ovarian Neoplasms - pathology Pathogens Science Science (multidisciplinary) Sequence Analysis, DNA - methods Tumors Whole Exome Sequencing - methods
ISSN:	2045-2322, 2045-2322
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Shrnutí:	Tumor heterogeneity is a consequence of clonal evolution, resulting in a fractal-like architecture with spatially separated main clones, sub-clones and single-cells. As sequencing an entire tumor is not feasible, we ask the question whether there is an optimal clinical sampling strategy that can handle heterogeneity and hypermutations? Here, we tested the effect of sample size, pooling strategy as well as sequencing depth using whole-exome sequencing of ovarian tumor specimens paired with normal blood samples. Our study has an emphasis on clinical application—hence we compared single biopsy, combined local biopsies and combined multi-regional biopsies. Our results show that sequencing from spatially neighboring regions show similar genetic compositions, with few private mutations. Pooling samples from multiple distinct regions of the primary tumor did not increase the overall number of identified mutations but may increase the robustness of detecting clonal mutations. Hypermutating tumors are a special case, since increasing sample size can easily dilute sub-clonal private mutations below detection thresholds. In summary, we compared the effects of sampling strategies (single biopsy, multiple local samples, pooled global sample) on mutation detection by next generation sequencing. In view of the limitations of present tools and technologies, only one sequencing run per sample combined with high coverage (100–300 ×) sequencing is affordable and practical, regardless of the number of samples taken from the same patient.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-020-71382-3