Tuesday, November 17, 2015 4:22:44 PM
Monday, November 16, 2015
A team of scientists from Australia, Canada, and the US published fascinating new work that may help explain gene expression patterns seen in prostate cancer. In the course of the project, they used SMRT Sequencing and found a novel fusion transcript linking two genes with high sequence identity.
“Identification of a novel fusion transcript between human relaxin-1 (RLN1) and human relaxin-2 (RLN2) in prostate cancer” was published in Molecular and Cellular Endocrinology by lead author Gregor Tevz, senior author Colleen Nelson, and a number of collaborators. In it, the scientists attempted to untangle expression signals from two relaxin genes, which were formed by a duplication event sometime before humans and apes branched off. The genes play a role in reproduction and are most highly expressed in ovaries and prostate. “Outside normal physiology, RLN2 is a promoter of cancer progression in several different types of cancers,” the scientists note.
Previous studies were unable to distinguish between the two genes, so this team deployed long-read sequencing and the Iso-Seq method from PacBio to sort out reads from RLN1 and RLN2 in LNCaP cells. Using their results along with publicly available data, they made a number of discoveries. For one thing, they found that most prostate cancer cell lines underrepresent RLN1, which is highly expressed in both normal and cancerous tissue. “LNCaP cells best reflect the RLN1 expression observed in [prostate cancer] and is the most relevant cell line for the use in further studies of RLN1 biology,” the team reports.
They also detected a novel fusion transcript that incorporates large swaths of both RLN1 and RLN2, but were able to design primers to distinguish the fusion from the genes. “The fusion transcript encodes a putative RLN2 with a deleted secretory signal peptide indicating a potentially biologically important alteration,” the scientists write. They determined that RLN1 and the fusion transcript are inversely regulated by androgens, and suggest that follow-up studies will be helpful to elucidate the mechanisms governing this response.
While we’re on the subject of cancer, don’t forget that the abstract deadline for the 2016 AACR annual meeting is coming up on December 2. We’re already looking forward to hearing about more great discoveries at that conference!
http://www.pacb.com/blog/scientists-use-the-iso-seq-method-to-study-genes-linked-to-prostate-cancer/
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