Gene-Fusion Research Promising

In a finding that could lead to a new diagnostic test and treatments, researchers reported they have discovered a pattern of chromosomes and abnormal gene activity that occurs only in prostate cancer.

The researchers said the shuffling of chromosomes causes specific genes to merge, creating what scientists call a gene fusion. This in turn affects the production of proteins that control cell growth.

“The data in our study provides tantalizing evidence that gene fusion is the causative agent – the initiating event – in prostate cancer,” said Dr. Arul Chinnaiyan, a professor of pathology at the University of Michigan Medical School and senior author of the study published in the journal Science.

“It’s what drives the aberrant over-expression of cancer-causing genes and is the first step in the progression of tissue changes leading to prostate cancer,” he added.

Collaborating with researchers at Harvard University’s Brigham and Women’s Hospital, the University of Michigan scientists detected the unique molecular signature of the fused genes in a majority of prostate cancer tissue samples they studied but found no evidence of gene fusion in benign prostate tissue or samples that had undergone non-cancerous changes.

Just last month, Dr. Chinnaiyan’s team published a report describing another possible advance in prostate cancer screening using a set of 22 proteins that are specific to this form of cancer.

Prostate cancer is the second leading cause of cancer death among men, behind lung cancer. According to the Prostate Cancer Foundation, some 232,000 men will be diagnosed with the disease this year, and about 30,000 will die from it.

Rearrangements of chromosomes and fused genes have been spotted in blood cell cancers, like leukemia and lymphoma, and in Ewing’s sarcoma, but this is the first time they’ve been detected in a common solid tumor like prostate cancer, which develops in cells lining the prostate gland.

The genetic clutter created by tumors had hampered researchers searching for a pattern of fused genes. Tumors produce so many chromosomal abnormalities it is difficult to tell which are significant.

Dr. Chinnaiyan and his colleagues used a special analytical program to find high expression levels of certain “outlier” genes in previously collected genetic arrays and in six independent prostate cancer-profiling studies.

Among the top 10 outlier genes identified were two, called ERG and ETV1, that are known to be involved in the development of other types of cancer.

In laboratory analysis, the researchers found that “of 22 cases with high expression of ERG or ETV1, 91 percent showed evidence of fusion with (a prostate specific gene called) TMPRSS2,” said Scott Tomlins, a graduate student in pathology and first author of the paper. “Our results indicate that more than half of all prostate cancer cases have one of these two fusions.”

He added it’s likely that the prostate-specific gene also fuses with similar genes involved in regulating cell growth, “but we just haven’t found them yet.”

The main current prostate cancer screening test relies on measuring levels of toxins produced by a tumor, but it generates many false positives from growths that are benign. Getting a conclusive diagnosis is more than half the battle, because the tumors are slow to grow and relatively easy to treat. Eighty-four percent of all men diagnosed with prostate cancer survive at least 10 years.