Genetics of Autosomal Mosaic Chromosomal Alteration (mCA)

Overview

Journal J Hum Genet

Specialty Genetics

Date 2021 Jul 29

PMID 34321609

Citations 5

Authors

Xiaoxi Liu

Yoichiro Kamatani

Chikashi Terao

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Campbell C, Eichler E . Properties and rates of germline mutations in humans. Trends Genet. 2013; 29(10):575-84. PMC: 3785239. DOI: 10.1016/j.tig.2013.04.005. View

Nakatochi M, Kushima I, Ozaki N . Implications of germline copy-number variations in psychiatric disorders: review of large-scale genetic studies. J Hum Genet. 2020; 66(1):25-37. DOI: 10.1038/s10038-020-00838-1. View

Forsberg L, Gisselsson D, Dumanski J . Mosaicism in health and disease - clones picking up speed. Nat Rev Genet. 2016; 18(2):128-142. DOI: 10.1038/nrg.2016.145. View

Jung D, Giallourakis C, Mostoslavsky R, Alt F . Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus. Annu Rev Immunol. 2006; 24:541-70. DOI: 10.1146/annurev.immunol.23.021704.115830. View

DGama A, Walsh C . Somatic mosaicism and neurodevelopmental disease. Nat Neurosci. 2018; 21(11):1504-1514. DOI: 10.1038/s41593-018-0257-3. View

Van Horebeek L, Dubois B, Goris A . Somatic Variants: New Kids on the Block in Human Immunogenetics. Trends Genet. 2019; 35(12):935-947. DOI: 10.1016/j.tig.2019.09.005. View

Serra E, Schwerd T, Moutsianas L, Cavounidis A, Fachal L, Pandey S . Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease. Nat Commun. 2020; 11(1):995. PMC: 7035382. DOI: 10.1038/s41467-019-14275-y. View

Neven B, Magerus-Chatinet A, Florkin B, Gobert D, Lambotte O, De Somer L . A survey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation. Blood. 2011; 118(18):4798-807. DOI: 10.1182/blood-2011-04-347641. View

Boveri T . Concerning the origin of malignant tumours by Theodor Boveri. Translated and annotated by Henry Harris. J Cell Sci. 2008; 121 Suppl 1:1-84. DOI: 10.1242/jcs.025742. View

10.

Koretzky G . The legacy of the Philadelphia chromosome. J Clin Invest. 2007; 117(8):2030-2. PMC: 1934583. DOI: 10.1172/JCI33032. View

11.

Druker B, Guilhot F, OBrien S, Gathmann I, Kantarjian H, Gattermann N . Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006; 355(23):2408-17. DOI: 10.1056/NEJMoa062867. View

12.

Albertson D, Collins C, McCormick F, Gray J . Chromosome aberrations in solid tumors. Nat Genet. 2003; 34(4):369-76. DOI: 10.1038/ng1215. View

13.

Kou F, Wu L, Ren X, Yang L . Chromosome Abnormalities: New Insights into Their Clinical Significance in Cancer. Mol Ther Oncolytics. 2020; 17:562-570. PMC: 7321812. DOI: 10.1016/j.omto.2020.05.010. View

14.

Gerstung M, Jolly C, Leshchiner I, Dentro S, Gonzalez S, Rosebrock D . The evolutionary history of 2,658 cancers. Nature. 2020; 578(7793):122-128. PMC: 7054212. DOI: 10.1038/s41586-019-1907-7. View

15.

Jacobs K, Yeager M, Zhou W, Wacholder S, Wang Z, Rodriguez-Santiago B . Detectable clonal mosaicism and its relationship to aging and cancer. Nat Genet. 2012; 44(6):651-8. PMC: 3372921. DOI: 10.1038/ng.2270. View

16.

Laurie C, Laurie C, Rice K, Doheny K, Zelnick L, McHugh C . Detectable clonal mosaicism from birth to old age and its relationship to cancer. Nat Genet. 2012; 44(6):642-50. PMC: 3366033. DOI: 10.1038/ng.2271. View

17.

Loh P, Genovese G, Handsaker R, Finucane H, Reshef Y, Palamara P . Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations. Nature. 2018; 559(7714):350-355. PMC: 6054542. DOI: 10.1038/s41586-018-0321-x. View

18.

Machiela M, Zhou W, Karlins E, Sampson J, Freedman N, Yang Q . Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome. Nat Commun. 2016; 7:11843. PMC: 4909985. DOI: 10.1038/ncomms11843. View

19.

Terao C, Momozawa Y, Ishigaki K, Kawakami E, Akiyama M, Loh P . GWAS of mosaic loss of chromosome Y highlights genetic effects on blood cell differentiation. Nat Commun. 2019; 10(1):4719. PMC: 6797717. DOI: 10.1038/s41467-019-12705-5. View

20.

Thompson D, Genovese G, Halvardson J, Ulirsch J, Wright D, Terao C . Genetic predisposition to mosaic Y chromosome loss in blood. Nature. 2019; 575(7784):652-657. PMC: 6887549. DOI: 10.1038/s41586-019-1765-3. View