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KIT gene in pediatric osteosarcomas: Could it be a new therapeutic target?
Author(s) -
EntzWerle Natacha,
Gaub MariePierre,
Lavaux Thomas,
Marcellin Luc,
Metzger Nadia,
MarecBerard Perrine,
Schmitt Claudine,
Brugiere Laurence,
Kalifa Chantal,
Tabone MarieDominique,
Pacquement Hélène,
Gentet Philippe,
Lutz Patrick,
Oudet Pierre,
Babin Annie
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22593
Subject(s) - pdgfra , locus (genetics) , biology , exon , population , gene , cancer research , loss of heterozygosity , genetics , microbiology and biotechnology , medicine , allele , gist , environmental health , stromal cell
In our previous study, a frequent rearrangement at 4q12 has been identified by allelotyping in our large and homogeneous population of pediatric osteosarcomas and it was significantly linked to c‐kit protein overexpression. To confirm and understand the involvement of KIT in this tumor, the next step of the study was designed to detect the potential mutations of KIT gene by sequencing the frequently mutated exons 6, 8, 10, 11, 13, 17 and 21 and, in case of unmutated samples, to confirm the genomic amplifications of the wild‐type receptor by real‐time quantitative PCR (QPCR). A new microsatellite and QPCR targeting PDGFRA was also added to check the accuracy of the 4q11‐12 locus. These techniques were performed in 74 pediatric high‐grade osteosarcomas treated with the OS94 protocol. Surprisingly, no mutations were found, but, only DNA amplification of KIT gene in the entire population. PDGFRA gene QPCR revealed an unexpected result of predominant deletions in the rearranged tumors. All these results confirm the major role of the 4q11‐12 locus and specifically the involvement of c‐kit wild‐type receptor overexpression in pediatric osteosarcomas and leads us to believe that inhibitors targeting this receptor could have a therapeutic effect in a selected group of patients. © 2007 Wiley‐Liss, Inc.