Dr. Samuel Aparicio

As we grow and develop, our cells divide. With every cell division, the three billion “letters” of DNA that make up our genetic instructions have to be copied. However, the copying process is not always perfect, and sometimes the mutations or “spelling mistakes” can lead to cells growing completely out of control. Researchers know this is how cancer develops.

What cancer researchers have not yet been able to do is identify all of the specific mutations that cause a particular breast cancer to spread. Until now that is.

Wielding state of the art sequencing technology, Dr. Samuel Aparicio, head of the breast cancer research program at the BC Cancer Agency, has for the first time ever decoded the genetic evolution of a breast cancer tumour by mapping all three billion letters in the DNA sequence of two tumours from the same breast cancer patient – a primary tumour and a metastatic tumour that were biopsied nine years apart.

His discovery, published in the prestigious journal Nature in the Fall of 2009, was a surprise not only to him and his team, but the breast cancer research community around the world – the mutations in the tumours had dramatically shifted as the disease spread.

It has been traditionally assumed that tumours are uniform throughout, containing the same mutations in all of their cells. However, together with the BC Cancer Agency’s Genome Sciences Centre, Aparicio’s team found 32 mutations in the tumour that had metastasized, or spread, and only five of these mutations had also been present in the original tumour biopsied nine years earlier.

This truly groundbreaking discovery is unlocking the secrets of how cancer begins and spreads, pointing the way to the development of new breast cancer treatment targets and therapies.

"I never thought I would see this in my lifetime,” says Aparicio for whom this discovery has a particularly personal resonance. Aparicio has a wife and four daughters, as well as a mother who was diagnosed with breast cancer and eventually succumbed to the disease.

The discovery is not only a major scientific milestone for the BC Cancer Agency, but also a significant testimony to the power of philanthropy to fuel cancer research and drive new discoveries. While the BC Cancer Foundation has been the primary funder of Aparicio’s research, numerous agencies made the breakthrough possible, including the Canadian Breast Cancer Foundation, the Canadian Institutes for Health Research, Genome Canada and Genome BC, the Canadian Foundation for Innovation, and the Michael Smith Foundation for Health Research.

The former Cambridge University researcher made headlines when he came to Canada from England in 2005. Internationally renowned for his contributions to genomics and translational medicine, his appointment to the BC Cancer Agency – and to the position of the Nan and Lorraine Robertson Chair in Breast Cancer Research and Canada Research Chair in Molecular Oncology at the University of British Columbia – led to expectations of Canada pioneering a new era in breast cancer research. It turns out those expectations have been exceeded, and then some.

Aparicio’s discovery that breast cancer tumours can be heterogeneous, or composed of multiple different mutations, suggests that the disease is a moving target, which has profound implications on the way new drugs are developed and the way cancers are targeted in the future.

“Our finding highlights the need to target all breast tumour cells at an early stage of treatment, rather than treating the tumour as a single uniform mass,” he says.

“This is a watershed in our ability to understand the causes of breast cancer and to develop personalized medicines for our patients,” Aparicio adds. “This new understanding will open so many doors for future research.”

Aparicio next aims to complete a comprehensive genomic map of breast cancer based on 2000 cancers, focusing on sequencing the genomes of triple negative breast cancers, which are particularly aggressive, and for which there are far fewer treatment options than for other breast cancers.