BACKGROUND: Recent molecular characterization studies have identified clinically relevant molecular subtypes to coexist within the same histological entities of glioma. Comparative studies between serum-supplemented and serum-free (SF) culture conditions have demonstrated that SF conditions select for glioma stem-like cells, which superiorly conserve genomic alterations. However, neither the representation of molecular subtypes within SF culture assays nor the molecular distinctions between successful and nonsuccessful attempts have been elucidated. METHODS: A cohort of 261 glioma samples from varying histological grades was documented for SF culture success and clinical outcome. Gene expression and single nucleotide polymorphism arrays were interrogated on a panel of tumors for comparative analysis of SF+ (successful cultures) and SF- (unsuccessful cultures). RESULTS: SF culture outcome was correlated with tumor grade, while no relation was found between SF+ and patient overall survival. Copy number-based hierarchical clustering revealed an absolute separation between SF+ and SF- parental tumors. All SF+ cultures are derived from tumors that are isocitrate dehydrogenase 1 (IDH1) wild type, chromosome 7 amplified, and chromosome 10q deleted. SF- cultures derived from IDH1 mutant tumors demonstrated a fade-out of mutated cells during the first passages. SF+ tumors were enriched for The Cancer Genome Atlas Classical subtype and intrinsic glioma subtype-18. Comparative gene ontology analysis between SF+ and SF- tumors demonstrated enrichment for modules associated with extracellular matrix composition, Hox-gene signaling, and inflammation. CONCLUSION: SF cultures are derived from a subset of parental tumors with a shared molecular background including enrichment for extracellular matrix-associated gene modules. These results provide leads to develop enhanced culture protocols for glioma samples not propagatable under current SF conditions.
BACKGROUND: Recent molecular characterization studies have identified clinically relevant molecular subtypes to coexist within the same histological entities of glioma. Comparative studies between serum-supplemented and serum-free (SF) culture conditions have demonstrated that SF conditions select for glioma stem-like cells, which superiorly conserve genomic alterations. However, neither the representation of molecular subtypes within SF culture assays nor the molecular distinctions between successful and nonsuccessful attempts have been elucidated. METHODS: A cohort of 261 glioma samples from varying histological grades was documented for SF culture success and clinical outcome. Gene expression and single nucleotide polymorphism arrays were interrogated on a panel of tumors for comparative analysis of SF+ (successful cultures) and SF- (unsuccessful cultures). RESULTS: SF culture outcome was correlated with tumor grade, while no relation was found between SF+ and patient overall survival. Copy number-based hierarchical clustering revealed an absolute separation between SF+ and SF- parental tumors. All SF+ cultures are derived from tumors that are isocitrate dehydrogenase 1 (IDH1) wild type, chromosome 7 amplified, and chromosome 10q deleted. SF- cultures derived from IDH1 mutant tumors demonstrated a fade-out of mutated cells during the first passages. SF+ tumors were enriched for The Cancer Genome Atlas Classical subtype and intrinsic glioma subtype-18. Comparative gene ontology analysis between SF+ and SF- tumors demonstrated enrichment for modules associated with extracellular matrix composition, Hox-gene signaling, and inflammation. CONCLUSION: SF cultures are derived from a subset of parental tumors with a shared molecular background including enrichment for extracellular matrix-associated gene modules. These results provide leads to develop enhanced culture protocols for glioma samples not propagatable under current SF conditions.
Authors: H Artee Luchman; Owen D Stechishin; N Ha Dang; Michael D Blough; Charles Chesnelong; John J Kelly; Stephanie A Nguyen; Jennifer A Chan; Aalim M Weljie; J Gregory Cairncross; Samuel Weiss Journal: Neuro Oncol Date: 2011-12-13 Impact factor: 12.300
Authors: Glynn Dennis; Brad T Sherman; Douglas A Hosack; Jun Yang; Wei Gao; H Clifford Lane; Richard A Lempicki Journal: Genome Biol Date: 2003-04-03 Impact factor: 13.583
Authors: Alexander Schulte; Hauke S Günther; Tobias Martens; Svenja Zapf; Sabine Riethdorf; Clemens Wülfing; Malgorzata Stoupiec; Manfred Westphal; Katrin Lamszus Journal: Clin Cancer Res Date: 2012-02-07 Impact factor: 12.531
Authors: Catherine L Nutt; D R Mani; Rebecca A Betensky; Pablo Tamayo; J Gregory Cairncross; Christine Ladd; Ute Pohl; Christian Hartmann; Margaret E McLaughlin; Tracy T Batchelor; Peter M Black; Andreas von Deimling; Scott L Pomeroy; Todd R Golub; David N Louis Journal: Cancer Res Date: 2003-04-01 Impact factor: 12.701
Authors: Marco Gallo; Jenny Ho; Fiona J Coutinho; Robert Vanner; Lilian Lee; Renee Head; Erick K M Ling; Ian D Clarke; Peter B Dirks Journal: Cancer Res Date: 2012-10-29 Impact factor: 12.701
Authors: Dan Rohle; Janeta Popovici-Muller; Nicolaos Palaskas; Sevin Turcan; Christian Grommes; Carl Campos; Jennifer Tsoi; Owen Clark; Barbara Oldrini; Evangelia Komisopoulou; Kaiko Kunii; Alicia Pedraza; Stefanie Schalm; Lee Silverman; Alexandra Miller; Fang Wang; Hua Yang; Yue Chen; Andrew Kernytsky; Marc K Rosenblum; Wei Liu; Scott A Biller; Shinsan M Su; Cameron W Brennan; Timothy A Chan; Thomas G Graeber; Katharine E Yen; Ingo K Mellinghoff Journal: Science Date: 2013-04-04 Impact factor: 47.728
Authors: Lale Erdem-Eraslan; Lonneke A Gravendeel; Johan de Rooi; Paul H C Eilers; Ahmed Idbaih; Wim G M Spliet; Wilfred F A den Dunnen; Johannes L Teepen; Pieter Wesseling; Peter A E Sillevis Smitt; Johan M Kros; Thierry Gorlia; Martin J van den Bent; Pim J French Journal: J Clin Oncol Date: 2012-12-26 Impact factor: 44.544
Authors: Barbara Klink; Hrvoje Miletic; Daniel Stieber; Peter C Huszthy; Jaime Alberto Campos Valenzuela; Jaime Alberto Campos Valenzuela; Jörg Balss; Jian Wang; Manja Schubert; Per Øystein Sakariassen; Terje Sundstrøm; Anja Torsvik; Mads Aarhus; Rupavathana Mahesparan; Andreas von Deimling; Lars Kaderali; Simone P Niclou; Evelin Schröck; Rolf Bjerkvig; Janice M Nigro Journal: PLoS One Date: 2013-03-19 Impact factor: 3.240
Authors: Wouter B L van den Bossche; Anne Kleijn; Charlotte E Teunissen; Jane S A Voerman; Cristina Teodosio; David P Noske; Jacques J M van Dongen; Clemens M F Dirven; Martine L M Lamfers Journal: Neuro Oncol Date: 2018-10-09 Impact factor: 12.300
Authors: Mohan S Nandhu; Prajna Behera; Vivek Bhaskaran; Sharon L Longo; Lina M Barrera-Arenas; Sadhak Sengupta; Diego J Rodriguez-Gil; E Antonio Chiocca; Mariano S Viapiano Journal: Clin Cancer Res Date: 2017-11-16 Impact factor: 12.531
Authors: L M E Berghauser Pont; R K Balvers; J J Kloezeman; M O Nowicki; W van den Bossche; A Kremer; H Wakimoto; B G van den Hoogen; S Leenstra; C M F Dirven; E A Chiocca; S E Lawler; M L M Lamfers Journal: Gene Ther Date: 2015-07-21 Impact factor: 5.250
Authors: Lotte M E Berghauser Pont; Anne Kleijn; Jenneke J Kloezeman; Wouter van den Bossche; Johanna K Kaufmann; Jeroen de Vrij; Sieger Leenstra; Clemens M F Dirven; Martine L M Lamfers Journal: PLoS One Date: 2015-05-18 Impact factor: 3.240
Authors: Lotte M E Berghauser Pont; Jochem K H Spoor; Subramanian Venkatesan; Sigrid Swagemakers; Jenneke J Kloezeman; Clemens M F Dirven; Peter J van der Spek; Martine L M Lamfers; Sieger Leenstra Journal: Genes Cancer Date: 2014-11
Authors: Rutger K Balvers; Martine L M Lamfers; Jenneke J Kloezeman; Anne Kleijn; Lotte M E Berghauser Pont; Clemens M F Dirven; Sieger Leenstra Journal: J Transl Med Date: 2015-02-26 Impact factor: 5.531
Authors: A Kleijn; J J Kloezeman; R K Balvers; M van der Kaaij; C M F Dirven; S Leenstra; M L M Lamfers Journal: Stem Cells Int Date: 2016-05-05 Impact factor: 5.443