Dualistic classifications assign tumors arising from one tissue into two broad
types based on differences in histology or grade, growth parameters (e.g., hormone
dependence or independence), prognosis, or expression of specific markers. Genomic
analyses have allowed a more mechanistic expression of dualistic classification, so that
tumor types may be founded on functional differences in the genetics of their
development. This review considers the dualistic model of ovarian cancer, which is
based primarily on whether or not mutations in the TP53 gene appear in the chronology
of tumor progression. Type I ovarian cancers generally do not display mutations in the
TP53 gene, and, according to several criteria, they have developed in the context of a
relatively stable genome. In contrast, Type II ovarian cancers develop mutations in the
TP53 gene early in tumorigenesis, and the resulting genome destabilization becomes a
primary driver in tumorigenesis. Type I ovarian cancers generally are of lower grade
and display a less malignant phenotype than Type II ovarian cancers, despite the better
response of Type II ovarian cancers to certain chemotherapeutic regimens. Some
reports have shown that mutation of TP53 can occur, albeit rarely late in a putative
Type I progression, giving rise to an ovarian cancer with growth and survival
properties similar to a Type II cancer. Future work should apply principles of dualistic
cancer lineages acquired from ovarian and some other cancers (e.g., sporadic and
inflammatory bowel disease-associated colorectal cancer) to produce a unified model
applicable to the prognostication and development of therapeutics for all cancers.
Keywords: Dualistic tumor classification, Genomic destabilization, Type I
ovarian cancer, Type II ovarian cancer, TP53, Tumor progression.
