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Jan 28, 2009

Chromosomal Alterations Confirmed and New Ones Implicated in Cancer

  • A team of researchers using high-throughput transcriptome sequencing have uncovered new genomic alterations that lead to gene fusions in a breast cancer cell line. The group authenticated six inter-chromosomal changes and one intra-chromosomal change that have the potential to affect the protein-producing ability of at least nine genes.

    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. Investigators did identify a new gene called the sterile alpha motif domain containing 12 gene (SAMD12) as being involved in both inter- and intra-chromosomal rearrangements. While not previously thought to play a role in the development of cancer, this finding may implicate the gene in cancer.

    The researchers performed high-throughput transcriptome sequencing using 454 Life Sciences’ technology on the well-characterized breast cancer cell line, HCC1954. They generate more than half a million reads of cDNA sequences. From that, the team uncovered 496 sequences that indicate chromosomal translocations. Of those 496, the team characterized 208 as inter-chromosomal abnormalities and 210 as intra-chromosomal abnormalities. At that point the scientists performed validation experiments with control cell line HCC1954 BL.

    Besides the inter- and intra-chromosomal changes discovered, the researchers also found 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.

    “This approach reveals alterations in the cancer genome within the active genes of cancer cells,” remarks Robert Strausberg, Ph.D., deputy director of the J. Craig Venter Institute. “Through the comparison with related normal cells we can glean those that are specific to cancer cells, thereby revealing their unique biology, as well as suggesting new approaches to detection, diagnosis, and treatment of cancers

    Researchers from the J. Craig Venter Institute and the Ludwig Institute for Cancer Research collaborated on the study, which is published the week of January 26 in the early online edition the Proceedings of the National Academy of Sciences.

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