November 28, 2014

TORONTO – Professor Michael Moran, Senior Scientist in Molecular Structure & Function at The Hospital for Sick Children (SickKids) Research Institute, along with colleagues at SickKids, Princess Margaret Cancer Centre and University of Toronto, has published an article in Nature Communications, describing an unprecedented large-scale analysis of the molecular make-up of normal and cancerous lung tissue.

“Our understanding of cancer and other genetic diseases is being revolutionized by technological advances in DNA sequencing – the field of genomics,” Moran says. “The hope is that by reading the DNA sequence of a tumour, doctors will be able to precisely classify and treat the cancer based on its individualized set of DNA mutations.”

Moran, who is professor of molecular genetics at U of T, and Canada Research Chair in Molecular Signatures, and his colleagues reasoned that since DNA sequences (in other words, our genes) are simply the blueprint for the production of proteins, they would look for patterns among tumour proteins that differed from normal lung proteins.

To accomplish this they used an advanced technology called mass spectrometry in order to convert cancer proteins into ion beams, so they can be described at sub-atomic levels of resolution. The scientists were astonished to find sets of proteins that were distinctly different in subsets of lung tumours, and to discover that these protein signatures correlated with patient survival.

Their results indicate that in addition to accumulating DNA mutations, tumours also arise by remodelling of the “proteome,” a term that defines the tens of thousands of different proteins present inside each cell. 

Another unexpected finding by the Moran team was that the cancer signature proteins were all involved in controlling metabolism, that is, the chemistry within cells which is well known to be highly irregular in tumours. However, the genes encoding metabolism proteins are not typically mutated in cancers, and consequently altered metabolism has often been viewed as a consequence, rather than a cause of cancer. Since drugs are designed to target proteins, the investigators are optimistic this new knowledge will open new avenues to precisely classify and treat individual tumours according to their protein and metabolism signatures.

The research paper, which was published today, is entitled “Integrated Omic analysis of lung cancer reveals metabolism proteome signatures with prognostic impact.”

News release prepared by ScikKids