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Cancer Detective

CancerDetective

A simulation to learn
about cancer and mutations

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The branch of biology that studies the genomes of tumours is known as Cancer Genomics. Before explaining what Cancer Genomics is, let’s look at the basic structures of our bodies: the cells.

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Cells are the basic units of our bodies, the "building blocks of life".
They group in different parts of our bodies to form tissues and organs.
The nucleus, the “control center of the cell”, holds the genome, formed by long strings of DNA (a molecular code made of 4 letters called nucleotides), tightly packed in chromosomes.
The genome contains the information for the cell to carry out its multiple functions.
The genome contains genes, the “basic units of heredity”, some sort of instructions to form mostly proteins: the macromolecular machines that carry out most cellular functions.
The genes, encoded in DNA, are transcribed into RNA, the message that can leave the nucleus and be translated into proteins.

The DNA of our cells accumulates errors or mutations naturally during our life.
What are mutations and what effects do they have? What can cause them?

Mutations are errors or changes in the DNA sequence of a cell.
Most mutations do not affect proteins, but those that fall into genes that form proteins can result in mutant or aberrant proteins.
Mutations are created by many different mechanisms that we call mutational processes.
Some mutations are created by external factors such as UV light or smoking, and others are generated by internal cellular processes like ageing.
Mutant proteins are those that contain errors. Some errors can affect the function of the protein and disturb normal cellular functions.
For example, if a mutation affects a protein controlling cellular growth and cell division, cells can grow or proliferate more than usual.
Different cells have different mutations. When a cell contains a mutation that makes it grow and proliferate faster than its neighboring cells, we say that cell has a selective advantage to proliferate.
Mutations that confer selective advantage to a cell are called cancer driver mutations.
The genes or proteins that are affected by cancer driver mutations are called cancer driver genes or proteins.
Cancer is a group of diseases characterized by the uncontrolled growth and proliferation of cells within the body.
Cancers or malignant tumors can arise if cells accumulate 4-6 cancer driver mutations.

Cancer arises through the subsequent accumulation of cancer driver mutations that confer cells with an advantage to proliferate over its neighbours.

The tumors of different patients have different sets of driver mutations, which are the key alterations that control the development of cancers. Cancer cells' survival relies on the effect of driver mutations.
Targeted therapies can specifically kill cancer cells by acting on the effect of driver mutations.
Knowing the driver alterations in a patient gives us valuable information such as the type of therapy that can be beneficial for them.
Giving personalized treatments can improve the outcome of cancer patients. This is called precision cancer medicine.

The genomic alterations found in the tumors of cancer patients are different. Identifying cancer drivers in each patient can help to provide better treatments.

First, we need to know the mutations that are in the cancer genomes of many cancer patients.
Thanks to many patients and projects from around the globe, we have access to these data.
Second, we need computational tools that help us to identify which proteins are cancer drivers.
We have developed IntOGen, a unified resource that merges information from different statistical methods and identifies cancer driver proteins across many cancer types.
Then, BoostDM, a machine learning algorithm, can predict which mutations within cancer driver proteins are actually driver mutations.
Finally, we can use The Cancer Genome Interpreter, which is an algorithm that uses the data generated by IntOGen, BoostDM and other resources to inform us whether a mutation in a protein is a cancer driver and if there is a specific therapy for cancers with this alteration.

Finding cancer drivers is a challenge. Cancers have from 100 to 100,000 of mutations, but we know that only a small percentage of them are cancer drivers. So how can we find them?

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