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Research Teams at J. Craig Venter Institute and Ludwig Institute for Cancer Research Uncover New Chromosomal Alterations in Cancer Using Transcriptome Sequencing Approach
Date:1/27/2009

mining, the team uncovered 496 sequences that indicate chromosomal translocations. Of these 496, the team characterized 208 as inter-chromosomal abnormalities and 210 were intra-chromosomal abnormalities. From here the team performed more detailed validation experiments with a control cell line (HCC1954 BL).

Through further analysis the team confirmed six inter-chromosomal changes and one intra-chromosomal change that have the potential to affect the protein producing ability of at least nine genes. The researchers also discovered that chromosome 8 in the cancer cell line seemed to be very involved in some of the genomic rearrangements. This data confirms earlier studies showing that genomic instability in this area is implicated in breast and prostate cancers.

Most genes involved in the discovered chromosomal rearrangement events in this study have been implicated in cancers, such as the MRE11A protein that is associated with mutations in many types of tumors including in breast cancer. The team also identified the SAMD12 gene as being involved in both inter- and intra-chromosomal rearrangements. While not previously thought to play a role in the development of cancer, this study showed that this gene might be implicated in cancer.

The team concluded that transcriptome sequencing with next generation sequencing technologies such as the 454 Life Sciences platform is very adept at finding genomic rearrangements and mutations associated with cancers. With deeper sequencing coverage this approach could be a powerful and efficient way to discover all events associated with expressed genes including gene fusions, somatic mutations and alternative trans-splicing that lead to the development of cancer.

Robert Strausberg, Ph.D., Deputy Director of the JCVI and leader of the Human Genomic Medicine team noted, "This approach reveals alterations in the cancer genome within the active genes of cancer cells. Through t
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SOURCE J. Craig Venter Institute
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