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Somatic microsatellite mutations as molecular tumor clocks

Nature Medicine volume 2, pages 676–681 (1996)Cite this article

Abstract

Microsatellite (MS) mutations can potentially unravel the past of mutator phenotype tumors, with greater genetic diversity expected in older regions. Rapid clonal expansions of xenografts were characterized by relatively homogenous MS alleles, whereas greater diversity was observed in a colorectal cancer with the greatest variation in its adjacent adenoma. A subcutaneous lung cancer metastasis demonstrated diversity consistent with its one–month clinical duration and evidence of active mitosis during dormancy. The genetic legacy inherent to multistep tumorigenesis provides direct estimates of tumor ages, with up to thousands of cell divisions and high death rates necessary to yield the observed diversities. MS molecular tumor clocks have the unique potential to systematically reconstruct the early and occult evolution of individual human mutator phenotype tumors.

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Authors and Affiliations

  1. Department of Pathology, University of Southern California School of Medicine, 1200 North State Street, No. 736, Los Angeles, California, 90033, USA

    Darryl Shibata & Zhi-Hua Li

  2. Department of Preventive Medicine, University of Southern California, 1540 Alcazar Street #220, Los Angeles, California, 90033, USA

    William Navidi

  3. Department of Pathology, Haartman Institute, P.O. Box 21, FIN-00014

    Reijo Salovaara

  4. University of Helsinki, Finland

    Reijo Salovaara

  5. Department of Medical Genetics, Haartman Institute, P.O. Box 21, FIN-00014

    Lauri A. Aaltonen

  6. University of Helsinki, Finland

    Lauri A. Aaltonen

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  1. Darryl Shibata
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  4. Zhi-Hua Li
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  5. Lauri A. Aaltonen
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Shibata, D., Navidi, W., Salovaara, R. et al. Somatic microsatellite mutations as molecular tumor clocks. Nat Med 2, 676–681 (1996). https://doi.org/10.1038/nm0696-676

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