Paper published in PNAS found novel mutations involved in malignant pleural mesothelioma and that each tumor had a unique mutation profile.
Researchers from The International Mesothelioma Program at Brigham and Women’s Hospital (BWH) and Harvard Medical School are reportedly the first to characterize mutations in expressed genes unique to malignant pleural mesotheliomas (MPMs). The data revealed a number of genes that could be causally related to the cancer.
The scientists used Ultra-Deep 454 Sequencing, which uses 454 Life sciences’ long-read sequencing technology, to characterize the full complement of individual tumor mutations in expressed genes in four MPM tumors and two controls. The investigators chose a whole transcriptome based approach, where they used the genome sequencer system to sequence the mRNAs from expressed genes because this approach enriches for mutations in these genes.
Approximately 266 million bases of expressed genes were sequenced per patient and analyzed with Alpheus™ software. the National Center for Genome Resources (NCGR) officially launched Alpheus today. The software was developed in collaboration with BWH to pipeline ultrahigh-throughput DNA sequences, enabling comparisons between patients and with reference databases to identify candidate mutations.
Between the four MPM samples, 15 tumor-specific, nonsynonymous mutations were identified, none of which had previously been implicated in mesothelioma, according to the scientists. XRCC6, PDZK1IP1, ACTR1A, and AVEN were among the genes found with a causal relationship. These tumor-specific variations represent multiple types of mutations including somatic point mutations, RNA editing, loss of heterozygosity (LOH), and epigenetic silencing. The investigators also found that each mesothelioma tumor had a unique mutation profile.
The results were published in the February 25 issue of the Proceedings of the National Academy of Sciences.