title: Credentialing preclinical pediatric xenograft models using gene expression and tissue microarray analysis.
abstract: Human tumor xenografts have been used extensively for rapid screening of the efficacy of anticancer drugs for the past 35 years. The selection of appropriate xenograft models for drug testing has been largely empirical and has not incorporated a similarity to the tumor type of origin at the molecular level. This study is the first comprehensive analysis of the transcriptome of a large set of pediatric xenografts, which are currently used for preclinical drug testing. Suitable models representing the tumor type of origin were identified. It was found that the characteristic expression patterns of the primary tumors were maintained in the corresponding xenografts for the majority of samples. Because a prerequisite for developing rationally designed drugs is that the target is expressed at the protein level, we developed tissue arrays from these xenografts and corroborated that high mRNA levels yielded high protein levels for two tested genes. The web database and availability of tissue arrays will allow for the rapid confirmation of the expression of potential targets at both the mRNA and the protein level for molecularly targeted agents. The database will facilitate the identification of tumor markers predictive of response to tested agents as well as the discovery of new molecular targets.
authors.affiliation: Oncogenomics Section, Comparative Oncology Program, and Cell and Molecular Biology Section, Pediatric Oncology Branch.
authors.forename: Craig C
authors.initials: CC
authors.lastname: Whiteford
authors.forename: Sven
authors.initials: S
authors.lastname: Bilke
authors.forename: Braden T
authors.initials: BT
authors.lastname: Greer
authors.forename: Qingrong
authors.initials: Q
authors.lastname: Chen
authors.forename: Till A
authors.initials: TA
authors.lastname: Braunschweig
authors.forename: Nicola
authors.initials: N
authors.lastname: Cenacchi
authors.forename: Jun S
authors.initials: JS
authors.lastname: Wei
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Smith
authors.forename: Peter
authors.initials: P
authors.lastname: Houghton
authors.forename: Christopher
authors.initials: C
authors.lastname: Morton
authors.forename: C Patrick
authors.initials: CP
authors.lastname: Reynolds
authors.forename: Richard
authors.initials: R
authors.lastname: Lock
authors.forename: Richard
authors.initials: R
authors.lastname: Gorlick
authors.forename: Chand
authors.initials: C
authors.lastname: Khanna
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Thiele
authors.forename: Mikiko
authors.initials: M
authors.lastname: Takikita
authors.forename: Daniel
authors.initials: D
authors.lastname: Catchpoole
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
authors.forename: Javed
authors.initials: J
authors.lastname: Khan
mesh_terms: D045744:Cell Line, Tumor; D002648:Child; D016000:Cluster Analysis; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016571:Neural Networks, Computer; D020411:Oligonucleotide Array Sequence Analysis; D023041:Xenograft Model Antitumor Assays / Q000379:methods*