Geometry of Gene Expression Space of Wilms` Tumors From Human Patients

נעמי פודה-שקד ^1,2 Ariel Trink ³ Itamar Kanter ³ Achia Urbach ⁴ Benjamin Dekel ^1,2 Tomer Kalisky ³

¹Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel 52621, Ramat Gan, Israel
²Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel, Tel Aviv, Israel
³Department of Bioengineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat Gan, Israel 52900, Ramat Gan, Israel
⁴The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel 52900, Ramat Gan, Israel

Wilms` tumor is a pediatric malignancy that is thought to originate from faulty kidney development during the embryonic stage. However, there is a large variation between tumors from different patients in both histology and gene expression that is not well characterized. Here we use a meta-analysis of published microarray datasets to show that Favorable Histology Wilms` Tumors (FHWTs) fill a triangle-shaped continuum in gene expression space of which the vertices represent three idealized “archetypes”. We show that these archetypes have predominantly renal blastemal, stromal, and epithelial characteristics and that they correlate well with the three major lineages of the developing embryonic kidney. Moreover, we show that advanced stage tumors shift towards the renal blastemal archetype. These results illustrate the potential of this methodology for characterizing the cellular composition of Wilms` tumors and for assessing disease progression.