Effects of chemotherapy on the cytogenetic constitution of Wilms' tumor.

Abstract

The management of Wilms' tumors consists of a combination of surgery, chemotherapy, and possibly radiotherapy. To date, chemotherapy is being risk stratified according to histologic subtype and stage. Although the cytogenetic characteristics of Wilms' tumors are well established, the cytogenetic effects related to chemotherapy are widely unknown. We herein report on comparative genomic hybridization findings in 41 primary Wilms' tumors of blastemal type, of which 19 had received preoperative chemotherapy (PCT group) and 22 did not (non-PCT group). Overall, imbalances could be detected in 32 tumors, with +1q (17 cases), +7q (10 cases), +7p (6 cases), and -7p (6 cases) as the most common changes. Among these, +7q and -7p were both significantly associated with metastatic disease at the time of surgery (P = 0.002 and 0.007, respectively), and +7q was also associated with higher stage (stages III + IV; P = 0.003). There were significant differences in the cytogenetic constitution of tumors between the two treatment groups. As a trend, tumors in the preoperative-chemotherapy group had fewer changes (mean, 2.7) than those in the non-preoperative-chemotherapy group (mean, 3.8), and the frequencies of imbalances at 7p or +7q, respectively, were significantly lower compared with tumors in the non-preoperative-chemotherapy group (2 of 19 versus 10 of 22, P = 0.019; 1 of 19 versus 9 of 22, P = 0.011). In contrast, -1q was common in both the preop-CT group (10 of 19) and the non-preop-CT group (7 of 22). The results suggest that Wilms' tumor clones with +1q are not obliterated by preoperative chemotherapy, whereas cytogenetically more complex clones with +7q and/or imbalances at 7p seem more responsive and are more likely to be eliminated by chemotherapeutic treatment.

• Authors: Thorsten Schlomm, Bastian Gunawan, Hans-Jürgen Schulten, Björn Sander, Karthinathan Thangavelu, Norbert Graf, Ivo Leuschner, Rolf-Hermann Ringert, László Füzesi
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 11 Issue 12 Pg. 4382-7 (Jun 15 2005) ISSN: 1078-0432 [Print] United States
• PMID: 15958621 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents

Topics

• Adolescent
• Antineoplastic Agents (adverse effects, therapeutic use)
• Child
• Child, Preschool
• Chromosome Aberrations (chemically induced)
• Chromosomes, Human, Pair 1 (drug effects, genetics)
• Chromosomes, Human, Pair 7 (drug effects, genetics)
• Female
• Follow-Up Studies
• Humans
• Infant
• Male
• Neoplasm Staging
• Nucleic Acid Hybridization (methods)
• Survival Analysis
• Wilms Tumor (drug therapy, genetics, pathology)