think we are beginning to understand that
the same tumor in two different individuals
may not behave the same way. For certain
JAK2 [Janus kinase 2] mutations, for example,
particular germline polymorphisms
predispose for specific mutations. Then we
see epigenetic heterogeneity. This can be
associated with differentiation states, either
stem cell–like or more differentiated properties,
but also it might not necessarily be
differentiation‑related—for example, in cells
that acquire the ability to be drug resistant.
And then there is a phenotypic heterogeneity.
And that’s all just within one tumor. If
you’re talking about heterogeneity within
a patient, then you can add the metastatic
lesions as well.
A. John Iafrate: As a pathologist, I spend
my time looking at human tumors, most
of which are heterogeneous
at the
morphological level
and are a mix of different
types of cells.
Lung cancer is a
great example. The
most common histologic
diagnosis for
lung cancer is lung
adenocarcinoma,
mixed subtype. By
mixed subtype, that
means a pathologist
will look at it and see
at least two, and possibly three or four different
morphologies in a single tumor. There is
likely an underlying epigenetic cause for this
morphologic heterogeneity. One region will
look really distinct from the other, and when
the tumor metastasizes/recurs, the morphology
may look like one or another part of the
tumor.
Acknowledging this common existence
of morphological heterogene-