Abstract
Smokeless tobacco associated Gingivobuccal squamous cell carcinoma (GB-SCC) is a major public health problem but available oral cancer cell lines are mostly from smoking associated tongue SCC raising the need for pertinent GB-SCC cell line models. As part of the International Cancer Genome Consortium (ICGC) Project, 4 novel cell lines, namely, Indian Tata Memorial Centre Oral Cancer (ITOC) −01 to −04 were established and characterized with conventional methods, karyotyping, ultrastructure, in vivo tumourigenicity, Whole exome sequencing (WES) and RNA sequencing. These hyperploid cell lines form xenografts in mice and show metabolically active and necrotic areas on fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging. WES of ITOC cell lines recapitulate the genomic tumor profile of ICGC GB-SCC database. We further identified smokeless tobacco associated genetic alterations (PCLO, FAT3 and SYNE2) and oncogenic PIK3CA mutation in GB-SCC cell lines. Transcriptome profiling identified deregulation of pathways commonly altered in cancer and down-regulation of arachidonic acid metabolism pathway, implying its possible role in GB-SCC. Clinical application of high throughput sequencing data depends on relevant cell line models to validate potential targets. Extensively characterized, these oral SCC cell lines are particularly suited for mechanistic studies and pre-clinical drug development for smokeless tobacco associated oral cancer.
Highlights
Advanced stage oral cancer with poor clinical outcome is a major public health problem in south Asian and east Asian countries where smokeless tobacco use is prevalent[1,2]
As part of our systematic efforts to establish relevant cell lines in the International Cancer Genome Consortium (ICGC) India oral cancer project, we have established and performed comprehensive molecular genetic characterization of 4 oral squamous cell carcinoma (OSCC) cell lines from tumour tissues obtained from tobacco chewing Indian patients
Detailed histological evaluation of OSCC tumors is tabulated in Supplementary Table S1
Summary
Advanced stage oral cancer with poor clinical outcome is a major public health problem in south Asian and east Asian countries where smokeless tobacco use is prevalent[1,2]. As part of our systematic efforts to establish relevant cell lines in the ICGC India oral cancer project, we have established and performed comprehensive molecular genetic characterization of 4 oral squamous cell carcinoma (OSCC) cell lines from tumour tissues obtained from tobacco chewing Indian patients. These cell lines are named ITOC-01, 02, 03 and 04, after the ethnic origin, institute and cancer site - Indian Tata Memorial Centre Oral Cancer (ITOC). To the best of our knowledge this is the first study from Indian subcontinent characterizing smokeless tobacco GB-SCC derived cell lines
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