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. 2020 Dec 23:7:533196.
doi: 10.3389/fmolb.2020.533196. eCollection 2020.

Biased Influences of Low Tumor Purity on Mutation Detection in Cancer

Jun Cheng  1 , Jun He  1 , Shanshan Wang  1 , Zhangxiang Zhao  2 , Haidan Yan  1 , Qingzhou Guan  1 , Jing Li  1 , Zheng Guo  1 , Lu Ao  1
Affiliations

Biased Influences of Low Tumor Purity on Mutation Detection in Cancer

Jun Cheng et al. Front Mol Biosci. .

Abstract

The non-cancerous components in tumor tissues, e.g., infiltrating stromal cells and immune cells, dilute tumor purity and might confound genomic mutation profile analyses and the identification of pathological biomarkers. It is necessary to systematically evaluate the influence of tumor purity. Here, using public gastric cancer samples from The Cancer Genome Atlas (TCGA), we firstly showed that numbers of mutation, separately called by four algorithms, were significant positively correlated with tumor purities (all p < 0.05, Spearman rank correlation). Similar results were also observed in other nine cancers from TCGA. Notably, the result was further confirmed by six in-house samples from two gastric cancer patients and five in-house samples from two colorectal cancer patients with different tumor purities. Furthermore, the metastasis mechanism of gastric cancer may be incorrectly characterized as numbers of mutation and tumor purities of 248 lymph node metastatic (N + M0) samples were both significantly lower than those of 121 non-metastatic (N0M0) samples (p < 0.05, Wilcoxon rank-sum test). Similar phenomena were also observed that tumor purities could confound the analysis of histological subtypes of cancer and the identification of microsatellite instability status (MSI) in both gastric and colon cancer. Finally, we suggested that the higher tumor purity, such as above 70%, rather than 60%, could be better to meet the requirement of mutation calling. In conclusion, the influence of tumor purity on the genomic mutation profile and pathological analyses should be fully considered in the further study.

Keywords: gastric cancer; microsatellite instability status; mutation calling algorithms; number of mutation; tumor purity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The result of mutation calling in different sampling positions. The number of mutation (or SNV) decreased as tumor purities decreased in two patients with gastric cancer (A,B) and two patients with colorectal cancer (C,D).
FIGURE 2
FIGURE 2
The influence of tumor purity on mutation detection between N0M0 and N + M0 samples. The differences of number of mutation or tumor purity between N0M0 and N + M0 samples (A,B), between N0M0 (N0M0-intes) and N + M0 (N + M0-intes) samples in intestinal gastric cancer (C,D), and between high-purity and low-purity samples (E,F). Outline points were deleted.
FIGURE 3
FIGURE 3
The influence of tumor purity on MSI status and pathological subtypes. (A) The differences of number of mutation or tumor purity between the diffuse and intestinal gastric cancer. (B) The differences of number of mutation or tumor purity between GBM and LGG or between LUAD and LUSC. (C) The differences of tumor purity between different MSI status both in gastric and colon cancer. Outline points were deleted.
See this image and copyright information in PMC

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