A study published in the September 20 issue of the online open-access journal PLoS Biology reveals that researchers discovered, during their study of ovarian cancer, that a substantial number of ovarian tumors show a gene that is closely related to the estrogen receptor. The gene is broken and fused to an adjacent gene by a chromosome rearrangement. This finding could help to understand how deadly tumors develop and spread.
The discovery of gene fusion in ovarian cancer could mean a new opportunity for scientists to specifically identify ovarian cancers early in their development potentially leading to the development of new treatments.
The researchers discovered the gene fusion searching through a great amount of data from "deep sequencing" of the genes active in ovarian tumors.
Patrick O. Brown, senior author of the study and Howard Hughes Medical Institute investigator, commented:
"Although this is the first time that a rearrangement of neighboring genes has been found to occur repeatedly in a cancer, we suspect that these local rearrangements may be more common and important than we had realized."
The most common type of ovarian cancer, serous ovarian cancer, is particularly lethal as it is usually only detected during the latter stages in its progression when the cancer has already spread to other tissues.
Researchers Julia Salzman, Robert J. Marinelli, Peter Wang and Brown discovered a recurrent gene fusion in about 15 % of serous ovarian cancer cases tested. The fusion occurs between ESRRA, a gene related to the estrogen receptor, and a nearby gene called C11orf20 and may provide an indication for the detection of some cancers at a curable stage.
As ovarian tumors in many patients share the same genetic change this may indicate their importance for the way the tumors behave. Brown commented that more study would reveal if this gene fusion contributes to the tumor's aggressive growth and spread.
The research that led to the discovery was performed at Stanford University School of Medicine by combining a relatively new "deep sequencing" technology with tools from genetics, computer science and statistics.
With funding supplied by the National Cancer Institute, the Howard Hughes Medical Institute and the Canary Foundation, a non-profit dedicated to developing technology for early detection of potentially deadly cancers, researchers set out to specifically look for evidence that the tumor had rearranged its DNA so that two distinct genes were now fused together in the tumor.
Julia Salzman, one of the researchers from the Stanford team explained:
"Many groups have hoped to find recurrent gene fusions in different cancers using deep sequencing, but it has been proved more difficult than expected. Doing the experiment to obtain the data is just the beginning - analyzing the data poses significant challenges. We spent months designing computer and statistical algorithms to sort out signal from noise".
Following this process, the researchers then faced the challenge to establish whether the finding was consistent or just a fluke. The presence of the gene fusion in multiple ovarian cancers was then independently confirmed by collaborators in the Canary network at the Fred Hutchinson Cancer Research Center in Seattle and the British Columbia Cancer Research Agency in Victoria, BC.
The discovery of the fusion between ESRRA and C11orf20 could reveal what happens as ovarian cancers develop, enabling researchers to investigate this in a new study. It also proves the principle that deep sequencing of the genes expressed in cancer can uncover recurrent gene fusions.
Future studies using similar methods will examine whether additional important genes can be found in ovarian tumors.
The study also has a much larger potential: the NIH, universities and other organizations have invested millions of dollars on deep sequencing of tumors.
Seeing that the resulting data is public, literally anyone can apply new methods to analyze it. Brown concluded saying that the work is ongoing: "We are testing our algorithms on publicly available data and hope it might lead to more discoveries."
Funding: Work in POB's lab was supported by the Canary Foundation, Howard Hughes Medical Institute, and US National Institutes of Health grant CA77097. POB is an investigator of the Howard Hughes Medical Institute. Work in CWD's lab was supported by the Pacific Ovarian Cancer Research Consortium and National Cancer Institute award number P50 CA083636. Work in BHN's lab was supported by the British Columbia Cancer Foundation and US Department of Defense grant OC080380. JSN is supported by a fellowship from the Canadian Institutes of Health Research. JS received partial salary support from National Science Foundation grant DMS-0940077. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Written by: Petra Rattue