The molecularly targeted
therapy crizotinib blocks
the abnormal protein that
leads to about 5 percent
of non-small cell lung
The Genetic Basis of Cancer
Changes, or mutations, in the genetic material of normal cells can disrupt the balance of factors
governing cell survival and division, and lead to cancer. This discovery, which was primarily enabled
through NIH funding, was one of the greatest research advances in the modern era.
The genetic material of a cell is made of deoxyribonucleic acid (DNA) strands, which are composed of
four units called bases. These bases are organized into genes, and the order, or sequence, of these
bases provides the code for producing the various proteins a cell uses to function. The organization
of DNA is similar to the way in which letters of the alphabet are carefully ordered to form words and
sentences (see Figure 4, p. 10).
The entirety of a person’s DNA is called a genome. Almost every cell in the body contains a copy of the
genome, which is packaged together with proteins called histones into thread-like structures called
chromosomes. In the analogy of the written word, the genome and chromosomes are similar to a story
and the chapters that make up that story, respectively (see Figure 4, p. 10).
Since a cell deciphers the DNA code to produce the proteins it needs to function, mutations in the code
can result in altered protein amounts or functions, ultimately leading to cancer (see Figure 5).
There are many different types of mutations that can cause cancer. These range in size from a single
base change (a letter is out of order or missing) to extra copies of a gene (a paragraph is repeated many
times) to the deletion of a large segment of a chromosome (part of a chapter is missing) (see Figure 6, p.
12). Further, chromosomes can break and recombine, resulting in the production of entirely new proteins,
like the one that causes most cases of chronic myelogenous leukemia (CML) and the one that leads to
about 5 percent of non-small cell lung carcinomas.
Figure 5: Deciphering the Genetic Code. The genome carries the DNA blueprint that is deciphered by cells to produce the various
proteins they need to function. Genes are decoded into proteins through an intermediate known as ribonucleic acid (RNA). Information
directing which genes should be accessible for decoding in different cells of the body is conveyed by special chemical tags on the DNA,
and by how the DNA is packaged with proteins into chromosomes, which also contains similar chemical marks. The pattern of these
chemical tags is called the epigenome of the cell. Cell activity, proteins, and a special form of RNA called non-coding RNA, can feedback
to alter each step of this process, and ultimately impact cell and tissue function in different ways.