부산대학교 도서관

The modern study of Wilms tumour was prompted nearly 50 years ago, when Alfred Knudson proposed the ‘two-hit’ model of tumour development. Since then, the efforts of researchers worldwide have substantially expanded our knowledge of Wilms tumour biology, including major advances in genetics — from cloning the first Wilms tumour gene to high-throughput studies that have revealed the genetic landscape of this tumour. These discoveries improve understanding of the embryonal origin of Wilms tumour, familial occurrences and associated syndromic conditions. Many efforts have been made to find and clinically apply prognostic biomarkers to Wilms tumour, for which outcomes are generally favourable, but treatment of some affected individuals remains challenging. Challenges are also posed by the intratumoural heterogeneity of biomarkers. Furthermore, preclinical models of Wilms tumour, from cell lines to organoid cultures, have evolved. Despite these many achievements, much still remains to be discovered: further molecular understanding of relapse in Wilms tumour and of the multiple origins of bilateral Wilms tumour are two examples of areas under active investigation. International collaboration, especially when large tumour series are required to obtain robust data, will help to answer some of the remaining unresolved questions.
Here, the authors describe the history of the efforts to expand knowledge of Wilms tumour biology, genetics, embryonal origin and associated syndromic and familial conditions, and to clinically apply prognostic biomarkers and development of preclinical models.
Key points: The genetic landscape of Wilms tumours has been deeply investigated, but the relationship to intratumoural heterogeneity and how abnormal nephrogenesis relates to malignant transformation to Wilms tumour are still being explored.Genetics of the classical syndromic conditions associated with Wilms tumour development have been described in detail, but whole-exome sequencing is revealing a wide range of constitutional mutations in children that lack any clear phenotype.Prognostic biomarkers are starting to be used in clinical practice and for risk stratification in trials, but more need to be identified and validated.Many complementary preclinical Wilms tumour models are now available.Efforts to explore the events that lead to aggressive and/or recurrent disease are needed.Worldwide international collaborations between experts in the field have been established.