Gain of MYCN region in a Wilms tumor-derived xenotransplanted cell line.
Wilms tumor is one of the most common pediatric malignant tumors of the kidney. Although the WT1 gene, located at 11p13, has been proven to be implicated in the development of Wilms tumor, other genes such as MYCN are also involved. The purpose of this study is to genetically characterize a Wilms tumor metastasis xenotransplanted in nude mice. Immunogenotype evolution of the xenografts material was monitored for 29 months using molecular techniques, fluorescent in situ hybridization and multiplex ligation-dependent probe amplification, in addition to immunohistochemistry in tissue microarrays. Genetic alterations present in the original tumor and retained in the xenotransplanted tumor were located in +1q, +3, +6, -7p, +7q, +8, -9p, +9q, +12. The multiplex ligation-dependent probe amplification detected a nondeleted status of genes located close to WT genes, except for a deletion of the EGFR gene (located at 7p11.2) and the GHRHR gene (located at 7p15), both flanking the WT5 gene. The MYCN gene (2p24 exon 3) and DDX1 gene (2p24 exons 2, 7, 15, and 24) were gained in passage 4 and the following passages. MYCN expression was positive from the beginning, without evidence of MYCN gain by fluorescent in situ hybridization. Histopathologic and growth rate changes were observed at those passages where low extra copy number of MYCN was present. In addition to other genetic abnormalities, the WT5 gene located at 7p13-14 is deleted and the MYCN gene gain began after 16 months in vivo evolution in athymic nude mice. MYCN is already used as a stratifying marker in neuroblastomas, and it may be also useful in implementing MYCN testing in prospective studies of Wilms tumors.
Noguera
Rosa
R
Department of Pathology, University of Valencia, Blasco Ibañez 17, Valencia, Spain. rosa.noguera@uv.es
Villamón
Eva
E
Berbegall
Ana
A
Machado
Isidro
I
Giner
Francisco
F
Tadeo
Irene
I
Navarro
Samuel
S
Llombart-Bosch
Antonio
A
D000818:Animals; D002675:Child, Preschool; D006801:Humans; D054643:INDEL Mutation; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008819:Mice, Nude; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques; D015513:Oncogene Proteins / Q000235:genetics*; D014183:Transplantation, Heterologous; D009396:Wilms Tumor / Q000473:pathology*
C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins