title: Genomic analysis and selected molecular pathways in rare cancers.
abstract: It is widely accepted that many cancers arise as a result of an acquired genomic instability and the subsequent evolution of tumor cells with variable patterns of selected and background aberrations. The presence and behaviors of distinct neoplastic cell populations within a patient's tumor may underlie multiple clinical phenotypes in cancers. A goal of many current cancer genome studies is the identification of recurring selected driver events that can be advanced for the development of personalized therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. In this paper, we highlight the use of DNA content-based flow sorting to identify and isolate DNA-diploid and DNA-aneuploid populations from tumor biopsies as a strategy to comprehensively study the genomic composition and behaviors of individual cancers in a series of rare solid tumors: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. We propose that the identification of highly selected genomic events in distinct tumor populations within each tumor can identify candidate driver events that can facilitate the development of novel, personalized treatment strategies for patients with cancer.
authors.affiliation: Norris Comprehensive Cancer Center, Division of Medical Oncology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Liu
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lenkiewicz
authors.forename: Lisa
authors.initials: L
authors.lastname: Evers
authors.forename: Tara
authors.initials: T
authors.lastname: Holley
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kiefer
authors.forename: Christian
authors.initials: C
authors.lastname: Ruiz
authors.forename: Katharina
authors.initials: K
authors.lastname: Glatz
authors.forename: Lukas
authors.initials: L
authors.lastname: Bubendorf
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Demeure
authors.forename: Cathy
authors.initials: C
authors.lastname: Eng
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ramanathan
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Von Hoff
authors.forename: Michael T
authors.initials: MT
authors.lastname: Barrett
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics; D000311:Adrenal Glands / Q000378:metabolism; D000368:Aged; D001003:Anal Canal / Q000378:metabolism; D000782:Aneuploidy; D001005:Anus Neoplasms / Q000235:genetics; D001650:Bile Duct Neoplasms / Q000235:genetics; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000235:genetics; D004247:DNA / Q000235:genetics*; D004171:Diploidy; D005260:Female; D023281:Genomics / Q000379:methods*; D006801:Humans; D007890:Leiomyosarcoma / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics*; D018358:Neuroendocrine Tumors / Q000235:genetics; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics
chemical_list: D004247:DNA