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Genetics of autosomal mosaic chromosomal alteration (mCA)

Journal of Human Genetics volume 66, pages 879–885 (2021)Cite this article

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Abstract

Mosaic chromosomal alterations (mCAs) are frequently observed in cancer cells and are regarded as one of the common features of cancers. Strikingly, accumulating studies demonstrated that mCAs are also prevalent in elderly individuals without cancer, implying mCA could be a feature of aging and not necessarily a cancerous state. However, the genetic basis of mCA has been mostly unknown. Recent studies of autosomal mCA based on biobank-scale datasets, including UK Biobank and Biobank Japan, provided a glimpse into the underlying genetic mechanism. In this concise review, we briefly introduced mCA, its link with cancer and aging, and the emerging genetic mechanisms of this phenomenon. We highlighted the following aspects: (1) the interplay between somatic and inherited germline mutations in generating mosaicism; (2) monogenic and polygenic architectures of mCA; and (3) population-specific profiles of mCA. We provided a future perspective emphasizing the need to understand the connection between mCA and other characteristics of aging, in particular, the epigenetic and immunologic features.

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Fig. 1: Illustration of different types of mCA.
Fig. 2: Frequency of detectable mCA in Biobank Japan (BBJ) dataset, stratified by age and sex.
Fig. 3: Frequencies of mCAs detected in autosomes.
Fig. 4: The monogenic and polygenic models underlying positive clone selection.

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Acknowledgements

We are grateful to Dr Yuki Ishikawa (RIKEN, IMS) for his critical reading and editing of the manuscript.

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Authors and Affiliations

  1. Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

    Xiaoxi Liu, Yoichiro Kamatani & Chikashi Terao

  2. Laboratory of Complex Trait Genomics, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan

    Yoichiro Kamatani

  3. Japan Clinical Research Center, Shizuoka General Hospital, Shizuoka, Japan

    Chikashi Terao

  4. Department of Applied Genetics, The School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan

    Chikashi Terao

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Correspondence to Chikashi Terao.

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Liu, X., Kamatani, Y. & Terao, C. Genetics of autosomal mosaic chromosomal alteration (mCA). J Hum Genet 66, 879–885 (2021). https://doi.org/10.1038/s10038-021-00964-4

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