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


RESULTS
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.


CONCLUSIONS
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.
Ludwig Collaborative Group, Department of Neurosurgery, Johns Hopkins University, 1550 Orleans Street, Baltimore, MD 21231, USA.
Qi
Q
Zhao
Ewen F
EF
Kirkness
Otavia L
OL
Caballero
Pedro A
PA
Galante
Raphael B
RB
Parmigiani
Lee
L
Edsall
Samantha
S
Kuan
Zhen
Z
Ye
Samuel
S
Levy
Ana Tereza R
AT
Vasconcelos
Bing
B
Ren
Sandro J
SJ
de Souza
Anamaria A
AA
Camargo
Andrew J G
AJ
Simpson
Robert L
RL
Strausberg
D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D019656:Loss of Heterozygosity; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction