Decade-long study helps unravel the complexities of cause and effect.

The largest ever study of cancer genetics, involving more than 1300 researchers across four continents, has catalogued a trove of cancer mutations in a vast, open access, computer cloud database.

The Pan-Cancer Analysis of Whole Genomes Consortium (PCAWG) gathered its findings meticulously over more than a decade to inform precision medicine, which aims to tailor treatment to a person’s specific cancer.

The results are detailed in six articles published in a special edition of the journal Nature.

“The entire Pan-Cancer work is helping to answer a long-standing medical difficulty: why two patients with what appears to be the same cancer can respond differently to the same drug,” says senior author Peter Campbell from the Wellcome Trust Sanger Institute in the UK.

“We show that the reasons for these different effects of treatment are written in the DNA,” he says.

The group used whole genome sequencing to tease out the unique genetics of tumours, analysing DNA from more than 2000 tumours of 38 types, including breast, brain, liver, prostate, lung and pancreas.

The researchers explain how the ruinous course of those cancers – the disease kills nearly 10 million a year and is the second biggest cause of death globally – follows the blueprint of Darwinian evolution.

Mutations arise in the genes of cells that confer a survival advantage, allowing those cells to replicate faster than their neighbours, breach tissue boundaries, and dodge the immune cells that try to wipe them out.

Mutations, the team says, come in two types. “Passenger” mutations are just along for the ride and don’t propel a tumour. “Driver” mutations, however, fuel the devastating fitness of cancer cells that enables their spread through the body.

Rooting out driver mutations and developing treatments that target them is the main game in cancer therapy – but where to look in a genome built from around three billion base pairs?

Read the full story in Cosmos magazine here