Tumor Suppressor Genes

Malignant tumors arise as a result of mutations
in three basic types of genes, DNA repair genes
(see p. 80 DNA repair), tumor suppressor genes,
and proto-oncogenes (see next plate). A single
mutation does not cause cancer. Rather several
mutations in different genes must accumulate
in one or several cells, which eventually lose
growth control in favor of aggressive growth
properties. Most mutations are somatic, i.e.,
limited to the neoplastic cells. A relatively small
subset ofmutations are present in the germline
(hereditary forms of cancer) and predispose the
individual to certain types of cancer.
Tumor suppressor genes encode proteins with
function in growth regulation or differentiation
pathways. Their name is derived from the observation
that one functional allele will
suppress tumor development even in the presence
of a mutation in the other allele (or its
loss). Thus, two mutational events are required
to release the growth-controlling function of a
tumor suppressor gene (see retinoblastoma,
p. 330). The two mutational events in a tumor
suppressor gene often become manifest in loss
of heterozygosity (LOH) in tumor cells (see B).
Tumor suppressor genes can be compared to
the brake of a car, cellular oncogenes