Allele loss at 16q defines poorer prognosis Wilms tumour irrespective of treatment approach in the UKW1-3 clinical trials: a Children's Cancer and Leukaemia Group (CCLG) Study.
Survival from Wilms tumour is excellent. Hence, better markers are required to restrict treatments causing late sequelae to those at highest risk of relapse. We investigated the prognostic significance of loss of heterozygosity (LOH) on 1p and 16q in 426 favourable histology Wilms tumours treated with either immediate nephrectomy (63%) or preoperative chemotherapy (37%). Four years RFS and OS were 84.6% and 92.0%, respectively. 10.3% tumours had LOH 1p, 14.6% LOH 16q, with 2.6% at both loci. In multivariate analysis, LOH 16q was associated with an increased risk of relapse (hazard ratio (HR) 2.69, 95%CI: 1.47-4.92) and death (HR 2.67, 95%CI: 1.17-6.06). LOH 1p showed no significant associations. These results were not influenced by treatment approach. LOH 16q is an adverse risk factor in favourable histology Wilms tumour, regardless of initial approach to therapy. Its relationship with histological risk groups defined after neo-adjuvant chemotherapy requires analysis in a larger series, and is the subject of the current SIOP WT 2001 trial.
Messahel
Boo
B
The Institute of Cancer Research, Section of Paediatric Oncology, Belmont, Sutton, Surrey, UK.
Williams
Richard
R
Ridolfi
Antonia
A
A'hern
Roger
R
Warren
William
W
Tinworth
Lorna
L
Hobson
Rachel
R
Al-Saadi
Reem
R
Whyman
Gavin
G
Brundler
Marie-Anne
MA
Kelsey
Anna
A
Sebire
Neil
N
Jones
Chris
C
Vujanic
Gordan
G
Pritchard-Jones
Kathy
K
D017024:Chemotherapy, Adjuvant; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats / Q000235:genetics; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009392:Nephrectomy; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome; D009396:Wilms Tumor / Q000235:genetics* / Q000473:pathology / Q000628:therapy