EURURO Vol. 72 No. 4

498 656

Interestingly, using whole-genome sequencing and bioin-
formatics analyses for subclonality, our group showed that
IDC and the adjacent glandular adenocarcinoma share an
original clonal ancestry before independent branching into
molecular subspecies B) . This suggests that the
occurrence and aggression of IDC are likely to be driven by a
series of genomic and epigenomic alterations in the prostate
gland during early tumorigenesis. If true, this would suggest
a novel model of prostate oncogenesis, whereby progression
from low- to high-risk disease in IDC-associated tumors may
not follow a linear sequential model, but may rather involve
a more acute change in evolutionary trajectory. That is
certainly the observation in BRCA2-mutant prostate cancers
harboring IDC, in which the early phase of tumor develop-
ment is uniquely characterized by enrichment of genetic and
epigenetic alterations in MED12 and MED12L . Important-
ly, these mutational events may explain the incremental
adverse prognosis conferred by IDC-positive compared to
IDC-negative BRCA2-mutant tumors .
In conclusion, Porter and colleagues have completed a
comprehensive review of the literature and provided us
with insights into the prevalence and potential clinical
implications of IDC in prostate cancer. These clinical data
emphasize the need to understand the biological bases for
IDC-CA aggression and possible field defects within the
prostate during oncogenesis. Future large-scale molecular
genetics studies will help to affirm the ‘‘ominous’’ nature of
this subpathology, and may underpin new approaches for
surveillance using modern imaging (eg, positron emission
tomography, functional magnetic resonance imaging), and
intensified treatment with novel therapies to improve cure
rates in men with IDC-CA prostate cancers.
Conflicts of interest: The authors have nothing to disclose.
Acknowledgments: The authors gratefully thank the Princess Margaret
Cancer Centre Foundation and the Radiation Medicine Program
Academic Enrichment Fund for support (to R.G.B.). Robert G. Bristow
is the recipient of a Canadian Cancer Society research scientist award.
Melvin L.K. Chua is supported by a National Medical Research Council of
Singapore transition award.
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