title: Aberrations of the CHK2 gene are rare in pediatric solid tumors.
abstract: In pediatric solid tumors, such as neuroblastoma (NB), it has been reported that the frequency of TP53 gene alterations is lower than that in adult tumors, suggesting that other tumor suppressor genes may play more important roles in the development of pediatric solid tumors. The CHK2 gene, whose product is a checkpoint kinase that plays a central role in DNA damage response and acts upstream of TP53, has been found to be mutated in a subset of Li-Fraumeni syndrome without mutations of TP53 and in some other sporadic human tumors, earmarking this serine/threonine kinase as a candidate tumor suppressor gene. Thus, we analyzed the CHK2 gene to address whether it is a candidate tumor suppressor gene for pediatric solid tumors. We screened for mutations of the CHK2 gene in 25 NB, 8 rhbdomyosarcoma, 12 Ewing sarcoma, and 26 other pediatric solid tumor cell lines as well as 77 fresh tumors including two cases of multiple cancers. Using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis and reverse transcriptase (RT)-PCR-SSCP followed by direct sequence analysis, we detected only one missense mutation (S505T) in one NB cell line and two silent mutations in one NB cell line and one NB fresh tumor, respectively. Through RT-PCR and subcloning analysis, we detected a similar expression of the CHK2 gene in all of the NB cell lines and fresh tumors; however, we identified at least three isoforms of the CHK2 gene, two of which have not been reported previously. These results suggest that aberrations of the CHK2 gene are rare in pediatric solid tumors.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Yu Yan
authors.initials: YY
authors.lastname: Chen
authors.forename: Junko
authors.initials: J
authors.lastname: Takita
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Kohmei
authors.initials: K
authors.lastname: Ida
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Koh
authors.forename: Takashi
authors.initials: T
authors.lastname: Igarashi
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hanada
authors.forename: Akira
authors.initials: A
authors.lastname: Kikuchi
authors.forename: Yukichi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Toyoda
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D064447:Checkpoint Kinase 2; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D006801:Humans; D007223:Infant; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D011110:Polymorphism, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases