Genotypes versus phenotypes: The potential paradigm shift in the diagnosis and management of pediatric neoplasms

Abstract The gold standard of cancer diagnosis has long been based on histological characteristics. With the rapid advancement of genetic medicine, such standard algorithm of diagnostic approach is facing a challenge. The genetic findings have been changed from being a “supporting character” into the role of a “main character”. More and more disease diagnosis and classification has to be defined by genetic basis. In this article, we focus on the challenges in the field of pediatric oncology. We cited 2 scenarios where genetic information plays a pivotal role in identifying the underlying pathology. The first scenario is that same genetic mutation can lead to variable clinical phenotypes, this includes EWSR1‐PATZ1 fusion related neoplasms; BCOR neoplasms; and GATA‐2 deficiency related immunodeficiency and myelodysplastic syndrome. Another scenario is relatively more common that is the same clinical and histopathological phenotype with different underlying genotypes. The genotypes actually impact on the treatment response and outcome. We used medulloblastoma as an example. In fact, we can also find similar scenario in many pediatric cancers such as Ewing sarcoma, ependymoma, etc. The essence of this article is to remind clinicians of the rapid development in genetic medicine and it has been reshaping the landscape of the modern disease classification and therapeutic approach. In the near future, it may even lead to a paradigm shift in our disease diagnostic algorithm.