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Elucidating the cancer-specific genetic alteration spectrum of glioblastoma derived cell lines from whole exome and RNA sequencing

Patil, Vikas and Pal, Jagriti and Somasundaram, Kumaravel (2016) Elucidating the cancer-specific genetic alteration spectrum of glioblastoma derived cell lines from whole exome and RNA sequencing. In: ONCOTARGET, 6 (41). pp. 43452-43471.

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Abstract

Cell lines derived from tumor tissues have been used as a valuable system to study gene regulation and cancer development. Comprehensive characterization of the genetic background of cell lines could provide clues on novel genes responsible for carcinogenesis and help in choosing cell lines for particular studies. Here, we have carried out whole exome and RNA sequencing of commonly used glioblastoma (GBM) cell lines (U87, T98G, LN229, U343, U373 and LN18) to unearth single nucleotide variations (SNVs), indels, differential gene expression, gene fusions and RNA editing events. We obtained an average of 41,071 SNVs out of which 1,594 (3.88%) were potentially cancer-specific. The cell lines showed frequent SNVs and indels in some of the genes that are known to be altered in GBM-EGFR, TP53, PTEN, SPTA1 and NF1. Chromatin modifying genes-ATRX, MLL3, MLL4, SETD2 and SRCAP also showed alterations. While no cell line carried IDH1 mutations, five cell lines showed hTERT promoter activating mutations with a concomitant increase in hTERT transcript levels. Five significant gene fusions were found of which NUP93-CYB5B was validated. An average of 18,949 RNA editing events was also obtained. Thus we have generated a comprehensive catalogue of genetic alterations for six GBM cell lines.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the IMPACT JOURNALS LLC, 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
Keywords: glioblastoma; exome & RNA sequencing; cancer-specific mutations; gene fusions; RNA editing
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Depositing User: Id for Latest eprints
Date Deposited: 02 Apr 2016 09:57
Last Modified: 02 Apr 2016 09:57
URI: http://eprints.iisc.ac.in/id/eprint/53513

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