New prostate cancer gene fusion was found

By | January 20, 2012

Recently, a sequencing-based transcriptome studies have found a new prostate cancer gene fusions. The study by the University of Michigan research team completed their patients by cell lines and tumor samples were sequenced transcriptome and found a new gene fusion in prostate cancer. Articles published in the January 11 the "Nature" online edition.
In the new gene fusion in prostate cancer, the researchers found a periodic read transcripts, known as SLC45A3-ELK4, and several mutations seems to be the integration of the individual. University of Michigan scientists Arul Chinnaiyan, but also the communication of the article, said: "cyclical convergence is considered to be a major cause of cancer. But we also found several other integration is unique to individual patients."
Chromosome rearrangements in cancer often leads to two separate genes together. In some cases, two genes linked coding region, resulting fusion protein. And sometimes lead to gene rearrangements in a gene regulatory elements under another gene, causing abnormal gene expression. Gene fusion with a variety of blood, bone marrow and soft tissue cancers such as leukemia, lymphoma and other related. Recently found that they began to appear in solid tumors.
To identify prostate cancer in the cancer-causing gene fusion, Chinnaiyan and his colleagues at the same time the use of the Roche 454 GS FLX and Illumina's Genome Analyzer sequencing for transcriptome analysis.
In order to verify their initial approach, the researchers conducted a series of verification experiments, look at whether chronic myeloid leukemia can be detected in the known gene fusion – BCR-ABL1.
CDNA library was constructed after the researchers on the Genome Analyzer has been in the millions of 36 – nucleotide sequence read length. They screened a long time to find out more than those containing a gene sequence. Information integration with the reference sequence, the team made the discovery of known and novel gene fusion approach. Reference sequence information generated from the 454 long-read sequencing long.
New prostate cancer gene fusion, they have also successfully found a prostate cancer tumor samples and cell lines TMPRSS2-ERG fusion. In this process, the researchers found a new reading of the fusion event. For example, in VcaP cell lines, they detected on chromosome 16 genes USP10 and ZDHHC7 two fusion occurred, and the gene on chromosome 2 HJURP fusion. LNCaP cell line at the same time, they found 14 genes on chromosome MIPOL1 DGKB gene on chromosome 7 in the fusion.
Next, the team turned to cell lines from tumor samples. Using transcriptome sequencing, the two are known to carry their assessment of TMPRSS2-ERG fusion in metastatic prostate cancer samples. Shown as expected, they found the TMPRSS2-ERG fusion, was also found that several new integration and read transcripts.
Which, SLC45A3-ELK4 seems to be a frequent visitor of prostate cancer, 20 metastatic tissues in the expression of this fusion 7. Authors, SLC45A3-ELK4 DNA integration does not seem to have caused the changes can be detected.
Chinnaiyan and his colleagues have also applied similar methods of breast cancer, lung cancer and melanoma of the gene fusion. They said: "This study using high throughput sequencing for the discovery of new gene fusion to establish a reliable method, showing the importance of mutations associated with cancer."

Original Search: Transcriptome sequencing to detect gene fusions in cancer

Abstract: Recurrent gene fusions, typically associated with haematological malignancies and rare bone and soft-tissue tumours1, have recently been described in common solid tumours2, 3, 4, 5, 6, 7, 8, 9. Here we use an integrative analysis of high-throughput long-and short-read transcriptome sequencing of cancer cells to discover novel gene fusions. As a proof of concept, we successfully used integrative transcriptome sequencing to 're-discover' the BCR-ABL1 (ref. 10) gene fusion in a chronic myelogenous leukaemia cell line and the TMPRSS2-ERG 2, 3 gene fusion in a prostate cancer cell line and tissues. Additionally, we nominated, and experimentally validated, novel gene fusions resulting in chimaeric transcripts in cancer cell lines and tumours. Taken together , this study establishes a robust pipeline for the discovery of novel gene chimaeras using high-throughput sequencing, opening up an important class of cancer-related mutations for comprehensive characterization.

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