title: Deep clonal profiling of formalin fixed paraffin embedded clinical samples.
abstract: Formalin fixed paraffin embedded (FFPE) tissues are a vast resource of annotated clinical samples. As such, they represent highly desirable and informative materials for the application of high definition genomics for improved patient management and to advance the development of personalized therapeutics. However, a limitation of FFPE tissues is the variable quality of DNA extracted for analyses. Furthermore, admixtures of non-tumor and polyclonal neoplastic cell populations limit the number of biopsies that can be studied and make it difficult to define cancer genomes in patient samples. To exploit these valuable tissues we applied flow cytometry-based methods to isolate pure populations of tumor cell nuclei from FFPE tissues and developed a methodology compatible with oligonucleotide array CGH and whole exome sequencing analyses. These were used to profile a variety of tumors (breast, brain, bladder, ovarian and pancreas) including the genomes and exomes of matching fresh frozen and FFPE pancreatic adenocarcinoma samples.
authors.affiliation: Clinical Translational Research Division, Translational Genomics Research Institute, Scottsdale, Arizona, United States of America.
authors.forename: Tara
authors.initials: T
authors.lastname: Holley
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lenkiewicz
authors.forename: Lisa
authors.initials: L
authors.lastname: Evers
authors.forename: Waibhav
authors.initials: W
authors.lastname: Tembe
authors.forename: Christian
authors.initials: C
authors.lastname: Ruiz
authors.forename: Joel R
authors.initials: JR
authors.lastname: Gsponer
authors.forename: Cyrill A
authors.initials: CA
authors.lastname: Rentsch
authors.forename: Lukas
authors.initials: L
authors.lastname: Bubendorf
authors.forename: Mark
authors.initials: M
authors.lastname: Stapleton
authors.forename: Doug
authors.initials: D
authors.lastname: Amorese
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.forename: Heather E
authors.initials: HE
authors.lastname: Cunliffe
authors.forename: Ann E
authors.initials: AE
authors.lastname: McCullough
authors.forename: Barbara
authors.initials: B
authors.lastname: Pockaj
authors.forename: David
authors.initials: D
authors.lastname: Craig
authors.forename: John
authors.initials: J
authors.lastname: Carpten
authors.forename: Daniel
authors.initials: D
authors.lastname: Von Hoff
authors.forename: Christine
authors.initials: C
authors.lastname: Iacobuzio-Donahue
authors.forename: Michael T
authors.initials: MT
authors.lastname: Barrett
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D003001:Cloning, Molecular; D055028:Comparative Genomic Hybridization; D005557:Formaldehyde / Q000378:metabolism*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology; D016612:Paraffin Embedding; D017422:Sequence Analysis, DNA / Q000379:methods*; D016707:Tissue Fixation
chemical_list: D005557:Formaldehyde