Genetics of autosomal mosaic chromosomal alteration (mCA)

doi:10.1038/s10038-021-00964-4

Review

. 2021 Sep;66(9):879-885.

doi: 10.1038/s10038-021-00964-4. Epub 2021 Jul 28.

Genetics of autosomal mosaic chromosomal alteration (mCA)

Xiaoxi Liu¹, Yoichiro Kamatani^{1

2}, Chikashi Terao^{3

4

5}

Affiliations

¹ Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
² Laboratory of Complex Trait Genomics, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
³ Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. chikashi.terao@riken.jp.
⁴ Japan Clinical Research Center, Shizuoka General Hospital, Shizuoka, Japan. chikashi.terao@riken.jp.
⁵ Department of Applied Genetics, The School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan. chikashi.terao@riken.jp.

PMID: 34321609
DOI: 10.1038/s10038-021-00964-4

Review

Genetics of autosomal mosaic chromosomal alteration (mCA)

Xiaoxi Liu et al. J Hum Genet. 2021 Sep.

. 2021 Sep;66(9):879-885.

doi: 10.1038/s10038-021-00964-4. Epub 2021 Jul 28.

Authors

Xiaoxi Liu¹, Yoichiro Kamatani^{1

2}, Chikashi Terao^{3

4

5}

Affiliations

¹ Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
² Laboratory of Complex Trait Genomics, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
³ Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. chikashi.terao@riken.jp.
⁴ Japan Clinical Research Center, Shizuoka General Hospital, Shizuoka, Japan. chikashi.terao@riken.jp.
⁵ Department of Applied Genetics, The School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan. chikashi.terao@riken.jp.

PMID: 34321609
DOI: 10.1038/s10038-021-00964-4

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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References

1. Campbell CD, Eichler EE. Properties and rates of germline mutations in humans. Trends Genet. 2013;29:575–84. - PubMed - PMC - DOI
1. Nakatochi M, Kushima I, Ozaki N. Implications of germline copy-number variations in psychiatric disorders: review of large-scale genetic studies. J Hum Genet. 2021;66:25–37. - PubMed - DOI - PMC
1. Liu X, Takata S, Ashikawa K, Aoi T, Kosugi S, Terao C, et al. Prevalence and spectrum of pathogenic germline variants in Japanese patients with early-onset colorectal, breast, and prostate cancer. JCO Precis Oncol. 2020;4:183–91. https://doi.org/10.1200/PO.19.00224 .
1. Forsberg LA, Gisselsson D, Dumanski JP. Mosaicism in health and disease—clones picking up speed. Nat Rev Genet. 2017;18:128–42. - PubMed - DOI - PMC
1. Jung D, Giallourakis C, Mostoslavsky R, Alt FW. Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus. Annu Rev Immunol. 2006;24:541–70. - PubMed - DOI - PMC

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[1] Campbell CD, Eichler EE. Properties and rates of germline mutations in humans. Trends Genet. 2013;29:575–84. - PubMed - PMC - DOI

[2] Campbell CD, Eichler EE. Properties and rates of germline mutations in humans. Trends Genet. 2013;29:575–84. - PubMed - PMC - DOI

[3] Nakatochi M, Kushima I, Ozaki N. Implications of germline copy-number variations in psychiatric disorders: review of large-scale genetic studies. J Hum Genet. 2021;66:25–37. - PubMed - DOI - PMC

[4] Nakatochi M, Kushima I, Ozaki N. Implications of germline copy-number variations in psychiatric disorders: review of large-scale genetic studies. J Hum Genet. 2021;66:25–37. - PubMed - DOI - PMC

[5] Liu X, Takata S, Ashikawa K, Aoi T, Kosugi S, Terao C, et al. Prevalence and spectrum of pathogenic germline variants in Japanese patients with early-onset colorectal, breast, and prostate cancer. JCO Precis Oncol. 2020;4:183–91. https://doi.org/10.1200/PO.19.00224 .

[6] Liu X, Takata S, Ashikawa K, Aoi T, Kosugi S, Terao C, et al. Prevalence and spectrum of pathogenic germline variants in Japanese patients with early-onset colorectal, breast, and prostate cancer. JCO Precis Oncol. 2020;4:183–91. https://doi.org/10.1200/PO.19.00224 .

[7] Forsberg LA, Gisselsson D, Dumanski JP. Mosaicism in health and disease—clones picking up speed. Nat Rev Genet. 2017;18:128–42. - PubMed - DOI - PMC

[8] Forsberg LA, Gisselsson D, Dumanski JP. Mosaicism in health and disease—clones picking up speed. Nat Rev Genet. 2017;18:128–42. - PubMed - DOI - PMC

[9] Jung D, Giallourakis C, Mostoslavsky R, Alt FW. Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus. Annu Rev Immunol. 2006;24:541–70. - PubMed - DOI - PMC

[10] Jung D, Giallourakis C, Mostoslavsky R, Alt FW. Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus. Annu Rev Immunol. 2006;24:541–70. - PubMed - DOI - PMC

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Genetics of autosomal mosaic chromosomal alteration (mCA)

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Genetics of autosomal mosaic chromosomal alteration (mCA)

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Abstract

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