Wilms tumour risk markers (anaplasia, 1p/16q loss, 1q gain, SIOP and COG risk groups)

What is measured: the risk that a Wilms tumour will relapse. How: histology (favourable versus focal or diffuse anaplasia, the latter tied to TP53 mutation; in the SIOP system, which operates after four to six weeks of vincristine and actinomycin, the post-chemotherapy picture is graded low risk when completely necrotic, intermediate for regressive, epithelial, stromal, mixed and focal anaplastic types, and high risk for diffuse anaplasia and blastemal-type tumours), tumour DNA for loss of heterozygosity at 1p and 16q (in the COG system, loss of both in favourable-histology stages I to IV means augmented therapy), 1q gain (about 30 percent, adverse, now built into COG and SIOP UMBRELLA protocols), 11p15 loss of heterozygosity and TP53. Very low risk in COG is stage I favourable histology under age 2 with a tumour under 550 g, treated by nephrectomy alone. Germline testing (WT1, 11p15 imprinting disorders such as Beckwith-Wiedemann, DIS3L2) is offered when the tumour is bilateral, syndromic or in an infant, and bilateral disease is managed with nephron-sparing surgery. What a result changes: the intensity climbs from vincristine and actinomycin alone, through the addition of doxorubicin, to cyclophosphamide, carboplatin and etoposide with radiotherapy for anaplastic and other high-risk disease. Where it matters: Wilms tumour.