Not a day goes by without a new story about the environment. Although we often consider the environment on a global scale, cells in our body also have to contend with environmental factors. New studies from a team of researchers from the Research Institute of the MUHC and McGill University show that the environment surrounding breast cancer cells plays a crucial role in determining whether tumor cells grow and migrate or whether they fade away. Their study is the first to identify the genes behind this environmental control and correlate them with patient outcome. Their findings are published in this week’s issue of Nature Medicine.

“A tumour can not exist on its own. It has to be supported and nourished by the cell types around it, the microenvironment,” says senior author Dr Morag Park, Director of the molecular oncology group at the Research institute if the MUHC. “When we began this study there was little known about the importance of this microenvironment on cancer initiation and progression. We now know that this environment is pivotal; different patients have distinct tumour microenvironments at a gene level. Our findings show that the gene profile of these distinct microenvironments can be used to determine clinical outcome — who will fare well and who will not.”

Dr Park, a professor of oncology, biochemistry, and medicine at McGill University, and her team analyzed tissue from 53 breast cancer patients. They used a unique technique, laser capture microdissection (LCM), to separate tumour cells from microenvironment tissue. They compared the gene expression between the microenvironment tissue and controls using micro-array analysis. From thousands of genes they identified 163, which correlated with patient outcome. A good outcome was defined as having no tumour metastasis and tumour migration and non-responsiveness to therapy was considered poor outcome.

From the original 163 genes, the team further identified a panel of 26 specific genes that could be used to accurately predict clinical outcome. This 26 gene-profile, called the stromal derived prognostic predictor (SDPP), was used to predict outcome from a second set of beast cancer patients.

“We were able to show that the SDPP effectively predicts outcome in a second group of patients,” says Dr Park, “This panel accurately forecasted patient status, suggesting that this may be a promising diagnostic tool.

“Our next steps are to develop this 26-gene predictor into a functional test. We are currently working on this and we anticipate a product for clinical trials within a year,” adds Park.

“This work takes tremendous dedication and collaboration from a number of people including pathologists, surgeons, oncologists as well as researchers. I would like to thank the outstanding work done by G. Finak from the laboratory of Dr M. Hallett of McGill’s Computer Science Department, the breast surgeons of the MUHC, including Dr S. Meterissian, and by the Department of Pathology at McGill, where Dr A. Omeroglu works.”

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Case Western Reserve University School of Medicine researchers published a study in The American Journal of Human Genetics identifying the hereditary components of colorectal cancer (CRC.) “Identification of Susceptibility Genes for Cancer in a Genome-wide Scan: Results from the Colon Neoplasia Sibling Study” is the first large linkage study of families with CRC and colon polyps in the country. Because only five percent of CRC cases are due to known gene defects, this NIH-funded study is designed to identify the remaining CRC-related susceptibility genes. The team built on a previous study which identified a specific region on chromosome 9q that harbors a CRC susceptibility gene. Upon review of a whole genome scan of all chromosome pairs in 194 families, the researchers were able to identify additional CRC gene regions on chromosomes 1p, 15q, and 17p.

While the overall Case Western Reserve University School of Medicine study looked at families with colon cancer and colon polyps, the study also analyzed families with different clusters of cancer, such as CRC with multiple polyps and CRC with breast cancer. These different phenotypes appeared to link to different chromosomal regions, which the study teams says supports the idea of multiple susceptibility genes causing different types of cancers. These links will be further investigated in the next phase of the study.

“The goal of our study is to identify the CRC genes in susceptible patients to better understand who may be prone to develop CRC and why,” said Georgia L. Wiesner, M.D., lead author of “Identification of Susceptibility Genes for Cancer in a Genome-wide Scan: Results from the Colon Neoplasia Sibling Study.” “This study is step towards future the of genetic CRC testing.”

The genome-wide scan used in this study will help physicians elucidate the genetic factors in CRC in the future. Once the genes are identified, physicians will be able to use these genetic markers to identify “at risk” patients and to develop better cancer screening strategies, such as colonoscopies well before standard screening begins at age 50. Currently, without new gene tests, family history is the only tool to determine a person’s risk for CRC. Knowing the exact gene will allow physicians to better take care of CRC patients and lead to earlier screening.

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