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Our genes are falling apart with age: detectable mosaic events in large populations

Wednesday, September 13, 2017 — Poster Session II

3:30 p.m. – 5:00 p.m.
FAES Terrace


  • Mitchell J. Macheila
  • Weiyin Zhou
  • Neil Caporaso
  • Michael Dean
  • Susan M. Gapstur
  • Nathaniel Rothman
  • Victoria L. Stevens
  • Meredith Yeager
  • Stephen J. Chanock


Clonal mosaicism arises when a post-zygotic mutational event is detectable in subpopulations of cells as an alternative genotype while not present in the germline genome. Although described in a subset of pediatric disorders, new genomic technologies have detected higher than anticipated frequencies of clonal mosaicism in adult population studies, stimulating investigation as to how clonal mosaicism could contribute to chronic human diseases, such as cancer, diabetes and neurodegenerative disorders. The risk for mosaic events increases with age. Mosaic Y loss is observed in nearly 20% of men over 60 years of age. X chromosome mosaicism nearly always involves the inactive chromosome whereas mosaic deletions on 20q and 13q14 correspond to known regions, often mutated in myeloid neoplasms and chronic lymphocytic leukemia respectively. Early studies have characterized the spectrum of detectable mosaic alterations and have begun to investigate whether detectable mosaicism could be important as an overall biomarker for risk or in the case hematologic cancers, identification of preleukemic clones. Mounting evidence has provided new insights into possible mechanisms responsible for genome maintenance as well as identification of genomic regions most susceptible to age-related genomic instability. It is plausible that genetic mosaicism can serve as a sentinel marker for overall genomic integrity wherein an increase in detectible genetic mosaicism could be a biomarker for cancer risk. We are pursuing large studies in solid tumors and in hematologic cancers; the latter afford the opportunity to look at the dynamic of mutational steps leading to a cancer and, in doing so, could identify pre-leukemic markers. Moreover, our recent discovery of a region on chromosome 14 associated with Y chromosome mosaicism (the most common large clonal event reported so far) provides an opportunity to examine basic, underlying mechanisms of mosaicism.

Category: Institute, Center, and Scientific Directors