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Systematic detection of putative tumor suppressor genes through the combined use of exome and transcriptome sequencing

Qi Zhao1, Ewen F Kirkness2, Otavia L Caballero1, Pedro A Galante3, Raphael B Parmigiani3, Lee Edsall4, Samantha Kuan4, Zhen Ye4, Samuel Levy5, Ana Tereza R Vasconcelos6, Bing Ren4, Sandro J de Souza3, Anamaria A Camargo3, Andrew JG Simpson1* and Robert L Strausberg1*

Author Affiliations

1 Ludwig Collaborative Group, Department of Neurosurgery, Johns Hopkins University, 1550 Orleans Street, Baltimore, MD 21231, USA

2 J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD 20850, USA

3 Ludwig Institute for Cancer Research, São Paulo Branch at Hospital Alemão Oswaldo Cruz, Rua João Julião 245, 01323-903 São Paulo, Brazil

4 Ludwig Institute for Cancer Research, San Diego Branch, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA

5 Scripps Translational Science Institute, 3344 North Torrey Pines Court, La Jolla, CA 92037, USA

6 Laboratório Nacional de Computação Científica, Laboratório de Bioinformática, Av. Getúlio Vargas 333, Petrópolis, RJ 25651-075, Brazil

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Genome Biology 2010, 11:R114  doi:10.1186/gb-2010-11-11-r114

Published: 25 November 2010



To identify potential tumor suppressor genes, genome-wide data from exome and transcriptome sequencing were combined to search for genes with loss of heterozygosity and allele-specific expression. The analysis was conducted on the breast cancer cell line HCC1954, and a lymphoblast cell line from the same individual, HCC1954BL.


By comparing exome sequences from the two cell lines, we identified loss of heterozygosity events at 403 genes in HCC1954 and at one gene in HCC1954BL. The combination of exome and transcriptome sequence data also revealed 86 and 50 genes with allele specific expression events in HCC1954 and HCC1954BL, which comprise 5.4% and 2.6% of genes surveyed, respectively. Many of these genes identified by loss of heterozygosity and allele-specific expression are known or putative tumor suppressor genes, such as BRCA1, MSH3 and SETX, which participate in DNA repair pathways.


Our results demonstrate that the combined application of high throughput sequencing to exome and allele-specific transcriptome analysis can reveal genes with known tumor suppressor characteristics, and a shortlist of novel candidates for the study of tumor suppressor activities.