Cancer: somatic mosaicism and the age-incidence curves of death
In the first part, I discuss the role of somatic mosaicism in cancer and neurodegeneration. Each of our bodies (soma) is genetically mosaic. We begin life with a single cell by union of parental sperm and egg. That single initial cell divides to give rise to the approximately 50 trillion cells of a full-grown individual, a greater lineage of descent than all of the primates that have ever lived. The vast number of cell divisions means that a lot of errors (mutations) arise during the copying and transmission of DNA. Each of us has a different pattern of mosaic patches of mutant genes throughout our bodies, set primarily by the mutations that happen very early in life. Recent genomic studies have confirmed the expected high levels of somatic mutations within individuals. Going forward, the big questions concern the degree to which those early life somatic mutations explain the variability between individuals in the risk of disease later in life.
In the second part, I discuss the molecular and cellular reliability mechanisms that normally protect against cancer and how those mechanisms break down during progression to disease. My long-term goal is to link those mechanistic insights to the outcome that matters: the onset of cancer. At present, we have epidemiological data on the ages of cancer onset in different tissues, but the link between mechanistic understanding of process at the molecular level and the pattern of disease onset remains weak. This problem leads to deeper issues about the time course of failure in complex systems, and how universal invariant aspects of failure interact with specific processes to shape the observed curves of death for particular diseases.
See https://stevefrank.org for more information.