TY - JOUR
T1 - Genetically-defined novel oral squamous cell carcinoma cell lines for the development of molecular therapies
AU - Fadlullah, Muhammad Zaki Hidayatullah
AU - Chiang, Ivy Kim Ni
AU - Dionne, Kalen R.
AU - Yee, Pei San
AU - Gan, Chai Phei
AU - Sam, Kin Kit
AU - Tiong, Kai Hung
AU - Ng, Adrian Kwok Wen
AU - Martin, Daniel
AU - Lim, Kue Peng
AU - Kallarakkal, Thomas George
AU - Mustafa, Wan Mahadzir Wan
AU - Lau, Shin Hin
AU - Abraham, Mannil Thomas
AU - Zain, Rosnah Binti
AU - Rahman, Zainal Ariff Abdul
AU - Molinolo, Alfredo
AU - Patel, Vyomesh
AU - Gutkind, J. Silvio
AU - Tan, Aik Choon
AU - Cheong, Sok Ching
PY - 2016/5/10
Y1 - 2016/5/10
N2 - Emerging biological and translational insights from large sequencing efforts underscore the need for genetically-relevant cell lines to study the relationships between genomic alterations of tumors, and therapeutic dependencies. Here, we report a detailed characterization of a novel panel of clinically annotated oral squamous cell carcinoma (OSCC) cell lines, derived from patients with diverse ethnicity and risk habits. Molecular analysis by RNAseq and copy number alterations (CNA) identified that the cell lines harbour CNA that have been previously reported in OSCC, for example focal amplications in 3q, 7p, 8q, 11q, 20q and deletions in 3p, 5q, 8p, 18q. Similarly, our analysis identified the same cohort of frequently mutated genes previously reported in OSCC including TP53, CDKN2A, EPHA2, FAT1, NOTCH1, CASP8 and PIK3CA. Notably, we identified mutations (MLL4, USP9X, ARID2) in cell lines derived from betel quid users that may be associated with this specific risk factor. Gene expression profiles of the ORL lines also aligned with those reported for OSCC. By focusing on those gene expression signatures that are predictive of chemotherapeutic response, we observed that the ORL lines broadly clustered into three groups (cell cycle, xenobiotic metabolism, others). The ORL lines noted to be enriched in cell cycle genes responded preferentially to the CDK1 inhibitor RO3306, by MTT cell viability assay. Overall, our in-depth characterization of clinically annotated ORL lines provides new insight into the molecular alterations synonymous with OSCC, which can facilitate in the identification of biomarkers that can be used to guide diagnosis, prognosis, and treatment of OSCC.
AB - Emerging biological and translational insights from large sequencing efforts underscore the need for genetically-relevant cell lines to study the relationships between genomic alterations of tumors, and therapeutic dependencies. Here, we report a detailed characterization of a novel panel of clinically annotated oral squamous cell carcinoma (OSCC) cell lines, derived from patients with diverse ethnicity and risk habits. Molecular analysis by RNAseq and copy number alterations (CNA) identified that the cell lines harbour CNA that have been previously reported in OSCC, for example focal amplications in 3q, 7p, 8q, 11q, 20q and deletions in 3p, 5q, 8p, 18q. Similarly, our analysis identified the same cohort of frequently mutated genes previously reported in OSCC including TP53, CDKN2A, EPHA2, FAT1, NOTCH1, CASP8 and PIK3CA. Notably, we identified mutations (MLL4, USP9X, ARID2) in cell lines derived from betel quid users that may be associated with this specific risk factor. Gene expression profiles of the ORL lines also aligned with those reported for OSCC. By focusing on those gene expression signatures that are predictive of chemotherapeutic response, we observed that the ORL lines broadly clustered into three groups (cell cycle, xenobiotic metabolism, others). The ORL lines noted to be enriched in cell cycle genes responded preferentially to the CDK1 inhibitor RO3306, by MTT cell viability assay. Overall, our in-depth characterization of clinically annotated ORL lines provides new insight into the molecular alterations synonymous with OSCC, which can facilitate in the identification of biomarkers that can be used to guide diagnosis, prognosis, and treatment of OSCC.
KW - Cell lines
KW - Copy number alteration
KW - Gene expression
KW - Mutation
KW - Oral squamous cell carcinoma
UR - http://www.scopus.com/inward/record.url?scp=84968813578&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.8533
DO - 10.18632/oncotarget.8533
M3 - Article
C2 - 27050151
AN - SCOPUS:84968813578
VL - 7
SP - 27802
EP - 27818
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 19
ER -