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Discordance of Somatic Mutations Between Asian and Caucasian Patient Populations with Gastric Cancer

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Abstract

Background

Differences in response to cancer treatments have been observed among racially and ethnically diverse gastric cancer (GC) patient populations. In the era of targeted therapy, mutation profiling of cancer is a crucial aspect of making therapeutic decisions. Mapping driver gene mutations for the GC patient population as a whole has significant potential to advance precision therapy.

Methods

GC patients with sequencing data (N = 473) were obtained from The Cancer Genome Atlas (TCGA; n = 295), Moffitt Cancer Center Total Cancer Care™ (TCC; n = 33), and three published studies (n = 145). In addition, relevant somatic mutation frequency data were obtained from cBioPortal, the TCC database, and an in-house analysis tool, as well as relevant publications.

Results

We found that the somatic mutation rates of several driver genes vary significantly between GC patients of Asian and Caucasian descent, with substantial variation across different geographic regions. Non-parametric statistical tests were performed to examine the significant differences in protein-altering somatic mutations between Asian and Caucasian GC patient groups. The frequencies of somatic mutations of five genes were: APC (Asian: Caucasian 6.06 vs. 14.40%, p = 0.0076), ARIDIA (20.7 vs. 32.1%, p = 0.01), KMT2A (4.04 vs. 12.35%, p = 0.003), PIK3CA (9.6 vs. 18.52%, p = 0.01), and PTEN (2.52 vs. 9.05%, p = 0.008), showing significant differences between Asian and Caucasian GC patients.

Conclusions

Our study found significant differences in protein-altering somatic mutation frequencies in diverse geographic populations. In particular, we found that the somatic patterns may offer better insight and important opportunities for both targeted drug development and precision therapeutic strategies between Asian and Caucasian GC patients.

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Acknowledgements

The authors acknowledge the contributions of the investigators in the TCGA and TCC studies with regard to the recruitment of patients and sample acquisition. TCC is enabled, in part, by the generous support of the DeBartolo Family. We thank the many patients who so graciously provided data and tissue to the TCC Consortium. Our study also received valuable assistance from the Cancer Informatics and Collaborative Data Services Core Facilities at the H. Lee Moffitt Cancer Center and Research Institute, a National Cancer Institute-designated Comprehensive Cancer Center, supported under National Institutes of Health grant P30-CA76292.

Author Contribution

Conception and design: HLM, JKL, JKT, YH. Development of methodology: FJ, JKL, JKT, TCK. Acquisition of data: FJ, JKT, TCK. Analysis and interpretation of data (e.g. statistical analysis, biostatistics, computational analysis): FJ, JKT, JKL, HLM. Writing, review, and/or revision of the manuscript: FJ, HLM, JKT, JKL, HZ, TCK, YH. Administrative, technical, or material support (i.e. reporting or organizing data, constructing databases): FJ, YH, TCK. Study supervision: HLM, JKL, JKT, HZ, YH.

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Authors and Affiliations

  1. Institute for Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China

    Feifei Jia, Hong-Hao Zhou, Yi-Jing He & Howard L. McLeod

  2. Division of Population Science, DeBartolo Family Personalized Medicine Institute, Moffitt Cancer Center, Tampa, FL, USA

    Feifei Jia, Todd C. Knepper, Yi-Jing He & Howard L. McLeod

  3. Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL, USA

    Jamie K. Teer & Jae K. Lee

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  1. Feifei Jia
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Correspondence to Howard L. McLeod.

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Conflicts of interest

Feifei Jia, Jamie K.Teer, Todd C. Knepper, Jae K. Lee, Hong-Hao Zhou, Yi-Jing He, and Howard L. McLeod declare that they have no competing interests.

Ethical approval and informed consent

All patients declared informed consent and the studies were approved by the Moffitt Cancer Center.

Funding

Feifei Jia is supported by the China Scholarship Council. This work was supported in part by Moffitt Cancer Center CCSG (Cancer Center Support Grant) funding (P30-CA76292).

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Jia, F., Teer, J.K., Knepper, T.C. et al. Discordance of Somatic Mutations Between Asian and Caucasian Patient Populations with Gastric Cancer. Mol Diagn Ther 21, 179–185 (2017). https://doi.org/10.1007/s40291-016-0250-z

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