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

Author(s)

Correa, Bruna R. S. ^{[1, 2]} ; Hu, Joanna ^[3] ; Penalva, Luiz O. F. ^[4] ; Schlegel, Richard ^[5] ; Rimm, David L. ^[3] ; Galante, Pedro A. F. ^[2] ; Agarwal, Seema ^{[3, 5]}

Affiliation

^[1] Ctr Genom Regulat CRG, Barcelona 08003 - Spain

^[2] Hosp Sirio Libanes, Ctr Oncol Mol, BR-01308060 Sao Paulo, SP - Brazil

^[3] Yale Univ, Dept Pathol, New Haven, CT 06510 - USA

^[4] Childrens Canc Res Inst UTHSCSA, San Antonio, TX 78229 - USA

^[5] Georgetown Univ, Med Ctr, Dept Pathol, Ctr Cell Reprogramming, Washington, DC 20007 - USA

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 8, MAR 6 2018.
• Web of Science Citations: 10

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. (AU)

• FAPESP's process: 13/07159-5 - RNA-binding proteins and post-transcriptional variations: influence on glioblastoma multiforme development
• Grantee: Bruna Renata Silva Corrêa
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/25483-4 - Identification and functional analysis of RNA binding proteins associated with the development of glioblastoma multiform
• Grantee: Bruna Renata Silva Corrêa
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate