by ecancer reporter Janet Fricker

In a study based on the genetic finger print of tumours taken from 2000 breast cancers patients, researchers from the UK and Canada have reclassified breast cancer into 10 distinct categories of disease.

The landmark Cancer Research UK study, published online today in Nature, has been heralded as having the potential to create a new treatment paradigm that should allow doctors to eventually better tailor treatments to individual breast cancers patients.

In the international study researchers, led by Carlos Caldas (University of Cambridge) and Samuel Aparicio (University of British Columbia, Vancouver), first studied the DNA of the tumours.

Focusing on copy number variations (these affect large stretches of DNA) and single nucleotide polymorphisms (SNPs; these affect single bases), they compared tumour DNA with matched healthy tissue DNA to pinpoint the cancer-specific changes and compile ‘genetic maps’ for each tumour. Next, they analysed RNA to show whether genes were ‘on’ or ‘off’.

Combining all their data gave them a ‘high-resolution genetic profile ‘for each individual tumour on a remarkable scale.

The study was first undertaken in a sample of 1000 tumours, and then reproduced in a second sample of 1000 tumours. Since this retrospective study was undertaken on archived material, it enabled the investigators to know the treatment outcomes for patients at the time of the investigation.

The main results from the study showed:

• That the different genetic profiles of the tumours clustered into 10 distinctive subtypes that have never been defined before.
• Several completely new genes, including deletions in PPP2R2A, MTAP, and MAP2K4 that have never before been linked to breast cancer.
• The relationship between these genes and known cell signalling pathways – networks that control cell growth and division.

“Our results will pave the way for doctors in the future to diagnose the type of breast cancer a woman has, the types of drugs that will work, and those that won’t, in a much more precise way than is currently possible,” said Carlos Caldas. “This research won’t affect women diagnosed with breast cancer today. But in the future, breast cancer patients will receive treatment targeted to the genetic fingerprint of their tumour.”

Samuel Aparicio, co-lead author of the study, added, “The size of this study is unprecedented and provides insights into the disease such as the role of immune response, which will stimulate other avenues of research.”


Reference
C Curtis, S Shahm S Chin, et al. The genomic and transciptomatic architecture of 2,000 breast tumours reveals novel subgroups. Nature. doi:10.1038/nature10983