Source: Earthtimes.org February 26, 2008
BRANFORD, Conn. – (Business Wire) 454 Life Sciences, a part of Roche Applied Science, today announced that researchers from The International Mesothelioma Program at Brigham and Women’s Hospital and Harvard Medical School in Boston have used the 454 long-read sequencing technology to characterize for the first time mutations in expressed genes unique to malignant pleural mesotheliomas (MPMs). The 454 Sequencing system was used to comprehensively investigate the transcriptomes of 4 MPMs and two control tissues. The data revealed a number of genes which could be causally related to cancer including XRCC6, PDZK1IP1, ACTR1A, and AVEN. The study appeared today, in the Proceedings of the National Academy of Sciences.
Malignant pleural mesothelioma is a rapidly fatal cancer, whose genetic basis is unknown. In a majority of cases, MPM is related to previous exposure to asbestos. The aim of The International Mesothelioma Program is to understand the causative factors in the development of the disease and to translate their findings into improved therapy.
The study describes how researchers used Ultra-Deep 454 Sequencing to characterize the full compliment of individual tumor mutations in expressed genes in four MPM tumors and two controls. Between the four MPM samples, 15 tumor-specific, non-synonymous (protein altering) mutations were identified. These tumor-specific variations represent multiple types of mutations including somatic point mutations, RNA editing, Loss of Heterozygosity (LOH), and epigenetic silencing. Using the 454 Sequencing system, researchers detected single nucleotide variations with 96% sensitivity and 100% specificity. This body of work represents the first deep sequencing of the transcriptome of MPM tumor.
“Large scale sequencing of tumor transcriptomes may be useful for determining patient-specific mutational profiles, enabling discoveries that have the potential to impact individual patient care,” said Dr. David Sugarbaker, MD, lead author and Chief, Division of Thoracic Surgery at Brigham and Women’s Hospital, and founder of the International Mesothelioma Program. “We envision that this approach may ultimately form the basis of the molecular sub-typing of patients with cancer, allowing for therapy designed individually for each patient based on their mutational profile.”
Researchers chose a whole transcriptome based approach, where they used the Genome Sequencer System to sequence the messenger RNAs from expressed genes because this approach enriches for mutations in these genes, facilitating the identification of point mutations (variations in a single nucleotide), insertions and deletions, variant allele frequencies, haplotypes, and RNA editing. Furthermore, transcriptome sequencing with the Genome Sequencer System provides read-count based gene expression profiling.