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Expanding primary cells from mucoepidermoid and other salivary gland neoplasms for genetic and chemosensitivity testing

Ahmad M. Alamri, Xuefeng Liu, Jan K. Blancato, Bassem R. Haddad, Weisheng Wang, Xiaogang Zhong, Sujata Choudhary, Ewa Krawczyk, Bhaskar V. Kallakury, Bruce J. Davidson, View ORCID ProfilePriscilla A. Furth
doi: https://doi.org/10.1101/171652
Ahmad M. Alamri
Oncology, Georgetown University, Washington, DC, USA, King Khalid University, Abha, Saudi Arabia.
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  • For correspondence: ama282@georgetown.edu
Xuefeng Liu
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Jan K. Blancato
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Bassem R. Haddad
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Weisheng Wang
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Xiaogang Zhong
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Sujata Choudhary
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Ewa Krawczyk
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Bhaskar V. Kallakury
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Bruce J. Davidson
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Priscilla A. Furth
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  • ORCID record for Priscilla A. Furth
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Abstract

Restricted availability of cell and animal models is a rate-limiting step for investigation of salivary gland neoplasm pathophysiology and therapeutic response. Conditionally reprogrammed cell (CRC) technology enables establishment of primary epithelial cell cultures from patient material. This study tested a translational workflow for acquisition, expansion and testing of CRC-derived primary cultures of salivary gland neoplasms from patients presenting to an academic surgical practice. Results showed cultured cells were sufficient for epithelial cell-specific transcriptome characterization to detect candidate therapeutic pathways and fusion genes in addition to screening for cancer-risk-associated single nucleotide polymorphisms (SNPs) and driver gene mutations through exome sequencing. Focused study of primary cultures of a low-grade mucoepidermoid carcinoma demonstrated Amphiregulin-Mechanistic Target of Rapamycin-AKT/Protein kinase B (AKT) pathway activation, identified through bioinformatics and subsequently confirmed as present in primary tissue and preserved through different secondary 2D and 3D culture media and xenografts. Candidate therapeutic testing showed that the allosteric AKT inhibitor MK2206 reproducibly inhibited cell survival across different culture formats. In contrast, the cells appeared resistant to the adenosine triphosphate competitive AKT inhibitor GSK690693. Procedures employed here illustrate an approach for reproducibly obtaining material for pathophysiological studies of salivary gland neoplasms, and other less common epithelial cancer types, that can be executed without compromising pathological examination of patient specimens. The approach permits combined genetic and cell-based physiological and therapeutic investigations in addition to more traditional pathologic studies and can be used to build sustainable bio-banks for future inquiries.

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Posted August 08, 2017.
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Expanding primary cells from mucoepidermoid and other salivary gland neoplasms for genetic and chemosensitivity testing
Ahmad M. Alamri, Xuefeng Liu, Jan K. Blancato, Bassem R. Haddad, Weisheng Wang, Xiaogang Zhong, Sujata Choudhary, Ewa Krawczyk, Bhaskar V. Kallakury, Bruce J. Davidson, Priscilla A. Furth
bioRxiv 171652; doi: https://doi.org/10.1101/171652
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Expanding primary cells from mucoepidermoid and other salivary gland neoplasms for genetic and chemosensitivity testing
Ahmad M. Alamri, Xuefeng Liu, Jan K. Blancato, Bassem R. Haddad, Weisheng Wang, Xiaogang Zhong, Sujata Choudhary, Ewa Krawczyk, Bhaskar V. Kallakury, Bruce J. Davidson, Priscilla A. Furth
bioRxiv 171652; doi: https://doi.org/10.1101/171652

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