Introduction

Biological Foundations showed how a cell reads its genome to build proteins, and how a change in DNA, such as F508del in CFTR, can change a protein and the person who carries it. Cancer is what happens when changes like these build up in the genes that control how a cell grows and divides. The National Cancer Institute calls it a genetic disease, and notes that each person's cancer has its own combination of genetic changes, which keeps changing as the cancer grows. Even cells within the same tumor can differ (National Cancer Institute).

Because cancer starts with changes in DNA, sequencing has become one of the main ways to study it. The Cancer Genome Atlas, a program run by the National Cancer Institute and the National Human Genome Research Institute starting in 2006, characterized more than 20,000 samples across 33 cancer types, tumors alongside healthy tissue from the same patients. It produced over 2.5 petabytes of data, which remain public, and researchers routinely use them to build and test tools such as variant callers. Many of the examples later in this guide come from studies like it.

This chapter covers the biology you need to make sense of that data. It introduces the vocabulary the rest of the guide relies on, such as oncogenes, tumor suppressors, driver mutations and clones:

• What Is Cancer?: what the many kinds of cancer have in common, how one begins and how the main types are named.
• Hallmarks of Cancer: the abilities that cancer cells share, whatever tissue they start in.
• Oncogenes and Tumor Suppressors: the two main kinds of genes that drive cancer when they change, and how to tell the changes that drive a tumor from the ones that come along for the ride.
• Signaling Pathways: how a cell decides to divide, and how mutations jam those decisions.
• How Tumors Evolve: how a tumor branches into related groups of cells as it grows, and how to see them in sequencing data.
• Inherited Risk: variants people are born with that raise their chance of developing cancer.