New Type of Mutation Found -- MEDICA - World Forum for Medicine

New Type of Mutation Found

Mayo Clinic researchers have discovered a new class of molecular mutation in various forms of breast cancer, a finding that may shed new light on development and growth of different types of breast tumours. Called fusion transcripts, the mutated forms of RNA may also provide a way to identify tumour subtypes and offer new strategies to treat them, investigators say.

Their study is the first to systematically search for fusion genes and fusion transcripts linked to different types of breast tumours. Oncologists currently recognise three basic types of breast tumours — estrogen-receptor (ER)-positive, HER2-positive, and triple negative.

"But breast cancer is much more complex than indicated by these three subtypes, and one of the challenges of treating the disease is to identify gene markers that predict how a tumour will respond to a specific treatment," says Doctor Edith Perez of the Mayo Clinic Comprehensive Cancer Centre in Florida.

"The discovery of subtype-specific fusion transcripts in breast cancer represents a step in this direction," she says. "Our findings indicate that fusion transcripts are much more common in breast cancer than had been realised. They represent a new class of mutation whose role in breast cancer is not understood at all."

"Fusion transcripts have the power to produce proteins that are relevant to tumour development, growth, and sensitivity to treatment, so we may have a brand new set of genomic changes that may help us understand, and treat, breast cancer in a new way," says Doctor E. Aubrey Thompson. "This is a novel discovery that will now require additional investigation. We need to understand what these fusion transcripts and proteins are doing."

Fusion transcripts are created when chromosomes break apart and recombine, an event that commonly occurs in cancer cells. During this process, fusion genes are created when two halves of normal genes become linked. Fusion genes (DNA) create fusion transcripts (RNA), which then produce fusion proteins.

"Mistakes are made," Thompson says. "That is one of the salient properties of tumour cells, because they are defective in repairing damage to their genes.These mutated proteins may have an entirely new, cancer-promoting function, or they may interfere with normal cellular functions."

Fusion transcripts are common in blood cancers, such as leukaemia and lymphoma. Before this discovery, however, few were found in solid cancers such as breast tumours. “Because fusion genes, transcript, and protein are generally found only in tumours, they make ideal biomarkers to identify tumour cells”, Perez says.; Source: Mayo Clinic