Mutation analysis in WT1 in patients with Wilms' tumors
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170 Abstracts TELOMERIC FUSIONS IN A WILMS' TUMOR. Fett-Conte AC (1), Liedtke Jr H (1), Chaves H (1), Thom~ JA (1), ~.~(2). (1) Faculdade de Medicina, (2) Instituto de Bioci~ncias, Letras e Ci~ncias Exatas - UNESP, S~o Jos(~ do Rio Preto, SP, Brazil. Wilms' tumor is one of the most common abdominal malignant solid tumors of childhood and can arise from any portion of the kidney. Cytogenetic and molecular studies have shown that two regions of the short arm of chromosome 11, 11p13 and 11p15, are involved in Wilms' tumor development and possibly other regions also play a role in the development of this tumor. As a part of a cytogenetic study on childhood neoplasias, a Wilms' tumor has been analyzed using short-term cultures of collagenase disaggregated primary tumor. A total of 97 metaphases were partially or totally analyzed and the majority were polyploid. In addition to many sporadic structural and numerical aberrations, twenty-two recurrent abnormalities were detected in different cells from two or more culture flasks. The breakpoints were preferentially located on telomeric regions and gave rise to end-to-end polycentric chromosomes or rings. Telomeric fusions are rare events but have already been described in a few premalignant and malignant lesions. However, to our knowledge, this is the first description of its occurrence in Wilms' tumor. The present findings suggest that one or more factors involved in telomeric stability are possibly abnormal in that tumor. (Supported by CNPq, FAPESP and FUNDUNESP). MUTATION ANALYSIS IN WT1 IN PATIENTS WITH WILMS' TUMORS .~Dt~.~&3~,* Os6rio-Almeida, M.L.,* Boavida, M.G.,+ Silva, J.M.**,t Martins, A.G.# and Cowell J. ## Lab. Gen. Mol. FCT/UNL*, Mte Caparica; Lab. Gen. Hum., INSA+, Lisboa; Servigo Pediatria, HSM**, Lisboa; S4Sl, HDE#, Lisboa; Oncology Dept., Inst. Child Health##, London Evidence to suggest a genetic predisposition for Wilms' tumor (WT) comes from: I) rare patients carrying constitutional chromosome 1 l p deletions; 2) loss of heterozygosity in 11p in tumors and 3) familial occurrence of tumors. Also, a candidate Wilms' tumor gene (WT1) has recently been isolated in 11p13 (Call et al, 1990. Cell 61. 1257). Several germinal and somatic mutations have since been identified in this gene in patients with Wilms tumor (Pelletier et al, 1991. Cell, 67. 437; Pelletier, 1991. Nature 353. 435). We analysed 14 Wilms' tumors for mutations in WT1. The patients had sporadic Wilms tumors (12), Dennis-Drash syndrome (1) and WAGR (1). SSCP analysis was performed in every tumor for all 10 exons of WTI. PCR direct sequencing was used to further characterize the alterations found in SSCP patterns.
Transcript of Mutation analysis in WT1 in patients with Wilms' tumors
170 Abstracts
TELOMERIC FUSIONS IN A WILMS' TUMOR. Fett-Conte AC (1), Liedtke Jr H (1), Chaves H (1), Thom~ JA (1), ~ . ~ ( 2 ) . (1) Faculdade de Medicina, (2) Instituto de Bioci~ncias, Letras e Ci~ncias Exatas - UNESP, S~o Jos(~ do Rio Preto, SP, Brazil.
Wilms' tumor is one of the most common abdominal malignant solid tumors of childhood and can arise from any portion of the kidney. Cytogenetic and molecular studies have shown that two regions of the short arm of chromosome 11, 11p13 and 11p15, are involved in Wilms' tumor development and possibly other regions also play a role in the development of this tumor. As a part of a cytogenetic study on childhood neoplasias, a Wilms' tumor has been analyzed using short-term cultures of collagenase disaggregated primary tumor. A total of 97 metaphases were partially or totally analyzed and the majority were polyploid. In addition to many sporadic structural and numerical aberrations, twenty-two recurrent abnormalities were detected in different cells from two or more culture flasks. The breakpoints were preferentially located on telomeric regions and gave rise to end-to-end polycentric chromosomes or rings. Telomeric fusions are rare events but have already been described in a few premalignant and malignant lesions. However, to our knowledge, this is the first description of its occurrence in Wilms' tumor. The present findings suggest that one or more factors involved in telomeric stability are possibly abnormal in that tumor. (Supported by CNPq, FAPESP and FUNDUNESP).
MUTATION ANALYSIS IN WT1 IN PATIENTS WITH WILMS' TUMORS .~Dt~.~&3~,* Os6rio-Almeida, M.L.,* Boavida, M.G.,+ Silva, J.M.**,t Martins, A.G.# and Cowell J. ## Lab. Gen. Mol. FCT/UNL*, Mte Caparica; Lab. Gen. Hum., INSA+, Lisboa; Servigo Pediatria, HSM**, Lisboa; S4Sl, HDE#, Lisboa; Oncology Dept., Inst. Child Health##, London
Evidence to suggest a genetic predisposition for Wilms' tumor (WT) comes from: I) rare patients carrying constitutional chromosome 1 l p deletions; 2) loss of heterozygosity in 11p in tumors and 3) familial occurrence of tumors. Also, a candidate Wilms' tumor gene (WT1) has recently been isolated in 11p13 (Call et al, 1990. Cell 61. 1257). Several germinal and somatic mutations have since been identified in this gene in patients with Wilms tumor (Pelletier et al, 1991. Cell, 67. 437; Pelletier, 1991. Nature 353. 435). We analysed 14 Wilms' tumors for mutations in WT1. The patients had sporadic Wilms tumors (12), Dennis-Drash syndrome (1) and WAGR (1). SSCP analysis was performed in every tumor for all 10 exons of WTI. PCR direct sequencing was used to further characterize the alterations found in SSCP patterns.
