Genotypic and phenotypic classification of cancer: How should the impact of the two diagnostic approaches best be balanced?

Abstract

Neoplastic tumors are traditionally named based on their differentiation (i.e., which normal cells and tissues they resemble) and bodily site. In recent years, knowledge about the genetic basis of tumorigenesis has grown rapidly, and the new information has in several instances been incorporated into the very definition of cancerous entities. The proper contribution of the diseases' phenotype and genotype to what they are called and how they are delineated from one another has rarely been subjected to explicit reasoning, however, nor is it often made clear whether existing naming practices are founded on ontological or utilitarian grounds. We look at several examples of how the new cytogenetic and molecular genetic understanding of tumorigenesis has impacted oncological nomenclature in a significant manner, but also at counterexamples where no similar change has taken place. In all likelihood, more and more neoplastic diseases will in the future be defined and named based on their pathogenesis rather than their phenotype, not least because effective and specific drug therapies directed against the molecular change at the very heart of oncogenesis will increasingly become available. The fact that this shift in emphasis is primarily guided by utilitarian considerations rather than any perception of acquired genetic changes as somehow being more ontologically "profound" or "important" in tumorigenesis, is as it should be; both the phenotype and the genotype of tumors are key parameters across most of oncology and are likely to be retained as the basis of coexisting disease classifications for as long as we can foresee.

Identification of the TAF15–ZNF384 fusion gene in two new cases of acute lymphoblastic leukemia with a t(12;17)(p13;q12)

“…Today, most tumor classification systems are based on the morphologic appearance of the tumor cells and their tissue organization as it appears through the microscope. We hope that our findings will help identify additional diagnostic markers that can distinguish tumors based on their acquired mutations, as such a classification may reflect important tumor characteristics better than do their histological appearance (Brandal et al, 2010). Eventually, our hope is that a more profound understanding of disease-causing mutations will reveal new targets for specific treatments.…”

Genomic aberrations in pediatric gliomas and embryonal tumors

“…Furthermore, of the 17 examined tumors, one-third could not readily be grouped in accordance with the current WHO classification (2007), emphasizing the diagnostic challenges neuropathologists and clinicians face. This accentuates the call for pathogenetic classifications, an alternative grouping of tumors that could also hopefully provide information about prognosis as well as key insights into molecular disease mechanisms that may eventually be translated into more effective and individualized therapies (Brandal et al, 2010).…”

Genomic aberrations in diffuse low‐grade gliomas

“…Eventually, a full pathogenetic classification of tumors would be one of the aims, an alternative grouping of neoplastic processes that could hopefully provide both information about prognosis and key insights into more effective therapies in individual cases than the current morphologybased classification does (Brandal et al, 2010).…”