title: Detection of an atypical teratoid rhabdoid brain tumor gene deletion in circulating blood using next-generation sequencing.
abstract: Circulating biomarkers such as somatic chromosome mutations are novel diagnostic tools to detect cancer noninvasively. We describe focal deletions found in a patient with atypical teratoid rhabdoid tumor, a highly aggressive early childhood pediatric tumor. First, we used magnetic resonance imaging (MRI) and histopathology to study the tumor anatomy. Next, we used whole genome sequencing (Next Gen Sequencing) and Bioinformatics interrogation to discover the presence of 3 focal deletions in tumor tissue and 2 of these 3 focal deletions in patient's blood also. About 20% of the blood DNA sequencing reads matched the tumor DNA reads at the SMARCB1 gene locus. Circulating, tumor-specific DNA aberrations are a promising biomarker for atypical teratoid rhabdoid tumor patients. The high percentage of tumor DNA detected in blood indicates that either circulating brain tumor cells lyse in the blood or that contents of brain tumor cells traverse a possibly compromised blood-brain barrier in this patient.
authors.affiliation: Phoenix Children's Hospital, Phoenix, Arizona, USA TGen (Translational Genomics Institute), Phoenix, Arizona, USA.
authors.forename: Madhavi
authors.initials: M
authors.lastname: Chakravadhanula
authors.affiliation: TGen (Translational Genomics Institute), Phoenix, Arizona, USA.
authors.forename: Waibhav
authors.initials: W
authors.lastname: Tembe
authors.affiliation: TGen (Translational Genomics Institute), Phoenix, Arizona, USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.affiliation: Phoenix Children's Hospital, Phoenix, Arizona, USA.
authors.forename: David
authors.initials: D
authors.lastname: Carpentieri
authors.affiliation: TGen (Translational Genomics Institute), Phoenix, Arizona, USA.
authors.forename: Winnie S
authors.initials: WS
authors.lastname: Liang
authors.affiliation: TGen (Translational Genomics Institute), Phoenix, Arizona, USA.
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Bussey
authors.affiliation: TGen (Translational Genomics Institute), Phoenix, Arizona, USA.
authors.forename: John
authors.initials: J
authors.lastname: Carpten
authors.affiliation: TGen (Translational Genomics Institute), Phoenix, Arizona, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Berens
authors.affiliation: Phoenix Children's Hospital, Phoenix, Arizona, USA TGen (Translational Genomics Institute), Phoenix, Arizona, USA rbhardwaj@phoenixchildrens.com.
authors.forename: Ratan D
authors.initials: RD
authors.lastname: Bhardwaj
mesh_terms: D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000473:pathology / Q000601:surgery; D001932:Brain Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods*; D004268:DNA-Binding Proteins / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D008279:Magnetic Resonance Imaging; D018335:Rhabdoid Tumor / Q000097:blood* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000235:genetics
chemical_list: D015415:Biomarkers; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors
keywords:   SMARCB1 gene; biomarker; pediatric brain tumors