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Sci Rep. 2018 Mar 6;8(1):4097. doi: 10.1038/s41598-018-22427-1.

Patient-derived conditionally reprogrammed cells maintain intra-tumor genetic heterogeneity.

Author information

1
Centro de Oncologia Molecular - Hospital Sírio-Libanês, São Paulo, SP, 01308-060, Brazil.
2
Centre for Genomic Regulation (CRG), Barcelona, 08003, Spain.
3
Department of Pathology, Yale University, New Haven, CT, 06510, USA.
4
Children's Cancer Research Institute - UTHSCSA, San Antonio, TX, 78229, USA.
5
Department of Pathology, Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC, 20007, USA.
6
Centro de Oncologia Molecular - Hospital Sírio-Libanês, São Paulo, SP, 01308-060, Brazil. pgalante@mochsl.org.br.
7
Department of Pathology, Yale University, New Haven, CT, 06510, USA. sa1137@georgetown.edu.
8
Department of Pathology, Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC, 20007, USA. sa1137@georgetown.edu.

Abstract

Preclinical in vitro models provide an essential tool to study cancer cell biology as well as aid in translational research, including drug target identification and drug discovery efforts. For any model to be clinically relevant, it needs to recapitulate the biology and cell heterogeneity of the primary tumor. We recently developed and described a conditional reprogramming (CR) cell technology that addresses many of these needs and avoids the deficiencies of most current cancer cell lines, which are usually clonal in origin. Here, we used the CR cell method to generate a collection of patient-derived cell cultures from non-small cell lung cancers (NSCLC). Whole exome sequencing and copy number variations are used for the first time to address the capability of CR cells to keep their tumor-derived heterogeneity. Our results indicated that these primary cultures largely maintained the molecular characteristics of the original tumors. Using a mutant-allele tumor heterogeneity (MATH) score, we showed that CR cells are able to keep and maintain most of the intra-tumoral heterogeneity, suggesting oligoclonality of these cultures. CR cultures therefore represent a pre-clinical lung cancer model for future basic and translational studies.

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