Large Study of Breast Cancer Genomes Uncovers New Genes and Mutations

May 2, 2016
Large Study of Breast Cancer Genomes Uncovers New Genes and Mutations
Ernesto del Aguila III, NHGRI

A team of international researchers led by scientists at the Wellcome Trust Sanger Institute and the European Bioinformatics Institute (EMBL-EBI) recently completed the largest-ever study to sequence the whole genomes of breast cancers, with the published data being released online today. The news study has uncovered 5 new genes associated with breast cancer and 13 new mutational signatures that influence tumor development. These findings not only pinpoint where genetic variations in breast cancers occur, but should also provide valuable insight into the causes of breast tumors—demonstrating that breast cancer genomes are highly individual.

The findings from these studies were published today in two journals. The first was published in Nature through an article entitled “The somatic genetics of breast cancer revealed by 560 whole genome sequences” and the second was published in Nature Communications through an article entitled “The topography of mutational processes in breast cancer genomes.”

The researchers analyzed 560 breast cancer genomes from patients in the U.S., Europe, and Asia. The team hunted for mutations that encourage cancers to grow and looked for mutational signatures in each patient’s tumor. Interestingly, they found that women carrying the BRCA1 or BRCA2 gene, who therefore have increased risk of developing breast and ovarian cancer, had whole cancer genome profiles that were very different to other breast cancers and highly distinctive from one other. This discovery could be used to classify patients more accurately for treatment.

“In the future, we’d like to be able to profile individual cancer genomes so that we can identify the treatment most likely to be successful for a woman or man diagnosed with breast cancer,” explained lead author of the Nature paper Serena Nik-Zainal, Ph.D., group leader at the Sanger Institute. “It is a step closer to personalized healthcare for cancer.”

Each patient’s cancer genome provides a complete historical account of the genetic changes that person has acquired throughout life. As they develop from a fertilized egg into full adulthood, a person’s DNA gathers genetic changes along the way. Human DNA is constantly being damaged, either by things in the environment or simply from regular wear and tear in the cell. These mutations form patterns—mutational signatures—that can be detected, and give clues about the causes of cancer. So knowing exactly where the mutations occur within the breast cancer genome is critically important.

“We know that genetic changes and their position in the cancer genome influence how a person responds to a cancer therapy,” noted Ewan Birney, Ph.D., senior scientist, and director of EMBL-EBI. “For years, we have been trying to figure out if parts of DNA that don’t code for anything specific have a role in driving cancer development. This study gave us the first large-scale view of the rest of the genome, uncovering some new reasons why breast cancer arises. It also gave us an unexpected way to characterize the types of mutations that happen in certain breast cancers.”

Sir Michael Stratton, Ph.D., director of the Sanger Institute, added that “unpicking the genetic variations between cancers is crucial to developing improved therapies. This huge study, the largest of any one cancer type to date, gives insights into which genetic variations exist, and where they are in the genome. This has implications for other forms of cancer, too. The study itself shows it is possible to sequence individual cancer genomes, and this should lead to benefits for patients in the long term.”

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