Feb 6, 2020 - Science

Scientists map out and "carbon date" cancer genomes in huge studies

Illustration of a closed fist holding a DNA helix

Illustration: Aïda Amer/Axios

An international collaboration of scientists announced Wednesday they have mapped out the cancer genome and also developed a new method of "carbon dating" cancer tumors to determine what and when mutations occurred that led to a person's cancer.

Why it matters: This meta-analysis of the whole genome is the first building block of a knowledge base that the scientists hope will help clinicians determine the precise treatment needed by individual patients — assuming the costs of sequencing and running algorithm programs continue to decline.

Background: Most previous research has focused on the 1% of the cancer genome, or the "exome," which provides instructions for protein coding. This sequencing often reveals one or more mutations — often called driver mutations — which are targetable in roughly two-thirds of patients.

  • But, as Wellcome Sanger Institute's Peter Campbell pointed out, clinicians are often amazed at how two patients with identical tumors would respond to treatments in opposite ways, showing "just how different one person’s cancer genome is from another's."
  • Campbell is a member of the steering committee for the Pan-Cancer Project, which is the decade-long collaboration of over 1,300 scientists and clinicians from 37 countries that helped produce these studies.

What they did: As published in 23 papers in Nature and its related journals, the teams analyzed more than 2,600 genomes of 38 different tumor types, including liver and breast cancer.

  • They created one of the largest resources of primary cancer genomes.
  • They also launched 16 working groups that studied different aspects of cancer's development, causation, progression and classification.

What they found: The researchers discovered they were able to identify about 95% of the tumor samples, and that many have four or five driver mutations that can be targeted. They did not find any drivers for about 5% of the cases.

  • Sequencing both the coding and non-coding portions of the genome allowed them to find many of the small changes that had impact and could be new drug targets, they said.
  • They also increased scientific understanding of the types of pathways involved in specific cancers that can help guide treatment options.

Plus, they developed a way to "carbon date" cancer, or identify mutations that had occurred many years ago that later played a role in cancer forming. From this method, they found about 20% of mutations actually occur years before tumor formation, and that half of these happen in the same nine genes.

  • "It's often years to a decade before they get all of the numbers of mutations required to become a full-grown cancer," Campbell said.
  • It's possible that diagnostics seeking these early mutations could help prevent cancer.

Of note: Two commentaries were published along with the studies.

  • The News & Views piece points out the ability to process hundreds of terabytes of data over millions of hours in multiple data centers was due to cloud computing, saying it's a "prime example of how cloud computing can make international collaboration possible and help to advance data-intensive fields."
  • The Comment piece says the time is now to develop an international code of conduct for data sharing to protect individual's privacy and ensure compliance with developing international laws.

The big picture: This is an important step toward the eventual goal of precise medicine — where a patient's tumor can be sequenced, and combined with consideration of lifestyle and other factors, find a comparable case to better advise treatment regime.

  • The costs of both sequencing and running algorithms need to continue dropping, but Campbell said he hopes "in a few years, this will be much more accessible than now and much more widely used."

Go deeper: Cancer death rates drop by largest amount on record in U.S.

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