New Advances in Next Generation RNA Sequencing

Genetic sequencing determines the precise order of the molecules that make up our DNA and RNA, which in turn are the molecular “fingerprint” of tumour cells that allow for personalized medicine for individual patients. Now, a new way of analyzing genomic data from tumours may one day allow clinicians to treat each person’s cancer as its own unique disease.

In a recent paper published by Mount Sinai researchers led by Drs. Alex Zlotta and Jeff Wrana, the team used leading-edge molecular analysis to decode the genetic makeup of a bladder cancer patient’s tumour, with will be vital to the medical decisions that are being tailored for the individual patient.

The research team established the methods to sequence all of a tumour’s RNA (whole transcriptome RNA-Sequencing) from tumours preserved in formalin. Formalin is an organic compound useful for preserving samples. Tumours are then embedded in paraffin (FFPE), which allows for samples to be solidified so that analysis can be done. When the results were compared between matched, freshly frozen tumour samples and FFPE tumour samples, the team observed similar results between the two sample types.

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A war between cellular defenses and ancient pathogens may contribute to cancer

In a study published by Nature Communications, researchers at the University of Ottawa’s Faculty of Medicine uncovered a novel mechanism that controls genetic change. This mechanism has possible roles in evolution, drug resistance, as well as tumor formation in a significant proportion of breast and ovarian cancers.

Cancer cells often develop resistance to drugs, a major factor preventing the cure of many types of cancers. Current evidence suggests that cancers are caused by multiple genetic changes and that continued genetic change causes tumors to develop resistance to drug treatments.

The mechanism, discovered by the research team led by Derrick Gibbings, involves an ongoing war between a cellular degradation process called autophagy and ancient pathogens known as retrotransposons. Essentially, retrotransposons create mutations within the DNA and are responsible for a quarter of the genetic differences between two individuals.

“By mutating our DNA, retrotransposons have provided us with genes vital to important functions such as the formation of placenta. In fact, almost half our genome derives from retrotransposons. However, they can also create mutations that lead to drug resistance, cancers and other diseases,” says Gibbings, assistant professor of cellular and molecular medicine. “Mammals, including humans, could not have evolved without retrotransposons. But they’re both our enemy and our friend.”

The research team discovered that autophagy degrades retrotransposons and prevents them from creating new mutations in the genome. Autophagy is known to be insufficiently active in 35% to 70% of ovarian and breast cancer tumors. Gibbings’ team is currently following up on preliminary evidence that in breast cancer patients, retrotransposons become overactive and can affect the survival rate of these women.

“We now understand that retrotransposons have an impact on the creation and growth of tumors as well as the evolution of species. Our results suggest that autophagy helps buffer these processes,” says Gibbings. “This leads us to believe that by allowing autophagy to do its job, we may be able to slow tumors and their reappearance after chemotherapy through the use of some relatively benign drugs already being used to treat other medical conditions.”

Thanks to the University of Ottawa for contributing this story.

New DNA analysis technique promises speedier diagnosis

Researchers from McGill University and the Génome Québec Innovation Centre have achieved a technical breakthrough that should result in speedier diagnosis of cancer and various pre-natal conditions.

The key discovery, which is described online this week in the Proceedings of the National Academy of Sciences (PNAS), lies in a new tool developed by Professors Sabrina Leslie and Walter Reisner of McGill’s Physics Department and their collaborator Dr. Rob Sladek of the Génome Québec Innovation Centre. It allows researchers to load long strands of DNA into a tunable nanoscale imaging chamber in ways that maintain their structural identity and under conditions that are similar to those found in the human body.

This newly developed “Convex Lens-Induced Confinement” (CLIC) will permit researchers to rapidly map large genomes while at the same time clearly identifying specific gene sequences from single cells with single-molecule resolution, a process that is critical to diagnosing diseases like cancer.

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Can Bacteria Cause Breast Cancer?

A unique population of microbes in the female breast may lay the groundwork for understanding how this bacterial community contributes to health and disease, according to a new study out of Western University (London, Canada). The study titled “Microbiota of human breast tissue,” is now published online, in advance of the May issue of Applied and Environmental Microbiology.

The human body is home to a large and diverse population of bacteria with properties that are both harmful and beneficial to our health. Studies are revealing the presence of bacteria in unexpected sites.

This new research has uncovered bacteria in breast tissue associated with cancer. Forms of bacteria known as ‘Proteobacteria’ were the most abundant, potentially as they are able to metabolize the fatty tissue, said the paper’s first author, Camilla Urbaniak, a PhD student in the Department of Microbiology & Immunology. Her studies, under the supervision of Lawson Health Research Institute Scientist and Schulich School of Medicine & Dentistry Professor Gregor Reid, involved breast tissue from 81 women in Canada and Ireland. Ten of the women undergoing breast reduction acted as controls, with 71 having benign or cancerous tumors. Bacteria were found in and beside the tumours.

“Although we have not proven that bacteria cause cancer, or that certain types of bacteria actually may reduce the risk of cancer, the findings open a completely new avenue for this important disease,” said Reid. “Imagine if women have a microbiota in the breast that puts them at higher risk of cancer? Or, if various drugs such as antibiotics or birth control pills alter the types of bacteria and their risk of cancer?”

Thanks to the University of Western Ontario for contributing this story.

New Mount Sinai discovery maps cell growth processes useful for future cancer drug development

Researchers at Mount Sinai Hospital’s Lunenfeld-Tanenbaum Research Institute have made a new discovery regarding how normal cells communicate and control their growth. The novel findings have the potential to better inform the selection of cancer drug therapies in clinical trials, and to improve drug resistance in cancer patients.

Published in the prestigious journal Nature today, researchers in Dr. Anthony Pawson’s lab at the Lunenfeld-Tanenbaum Research Institute studied a cell growth trigger that is initiated by a protein which is often mutated in cancer. This protein, called epithelial growth factor receptor (EGFR), sits on the cell surface, and sends signals inside cells to control processes such as cell survival and expansion. The protein is an important target for cancer drug therapies.

Using targeted mass spectrometry, a cutting-edge technology, scientists in Dr. Pawson’s lab tracked the assembly of multiple proteins into signaling complexes from the moment the EGFR signal is turned ‘on’, to when the cell signal turns ‘off’. In cancer, the ‘off’ signal is often defective, leading to uncontrolled cell growth.

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