Page 71 - 20dynamics of cancer

56 CHAPTER 3

(a) (b) (c) (d)

Figure 3.5 Differences in success between lineages in a phylogeny influence
the shape of the tree. All trees shown with the ancestral cell of origin on the
left. Time increases from left to right. (a) Shape when all lineages survive. (b)
Tips that stop in the middle of the tree represent lineages that have gone extinct.
Some extinctions occur in this case, but many different lineages have survived
to the present. (c) Greater differential success between lineages; however, no
single winner emerges in any time period. (d) Only a single lineage survives over
time, shown in bold. In each time period, a single lineage gives rise to all sur-
vivors a few generations into the future. If major changes in progression cause
subsequent clonal expansions, each clonal expansion arising from a particular
cell, then the phylogeny will be dominated by a single lineage as in (d).

may then split off by seeding a few new stem lineages. The cycle of co-
alescence and splitting of lineages repeats. If early genetic changes in
cancer progression do not alter the normal pattern of cellular lineages,
then such changes accumulate in a dominant cell lineage of a crypt. A
different cell lineage usually dominates in each crypt (Kim and Shibata
2004). A tumor usually arises from a single crypt, so a single lineage
dominates early tumor evolution.
Only a few studies provide indirect information on cell lineages in
a growing primary tumor. Leukemias have been analyzed more than
solid tumors, because one can easily sample over time the evolving cells
in the blood. Among later-stage leukemias, only a small fraction of can-
cer cells have the ability to regenerate a tumor (Reya et al. 2001). These