The Cancer Genetics Clinic is part of Stanford's
Cancer Center, a National Cancer Institute-designated center
offering genetic counseling and testing for individuals concerned with
the risk of an inherited cancer predisposition. The clinic staff
includes medical oncologists, genetic counselors, and geneticists.
In order to understand the genetic mechanisms of how genes cause
cancer, it is important to review some basic genetic concepts. Genes
come in pairs, and work together to make a protein product. One member
of the gene pair comes from the mother, while the other member is
inherited from the father. Eggs and sperm are called "germ
cells." When an alteration or mutation in a gene is present in
the germ cells, it is referred to as a "germline mutation."
When a germline mutation is inherited, it is present in all body
cells. On the other hand, mutations that we are not born with, but
that occur by chance over time in cells of the body are said to be
"acquired." Acquired mutations are not present in all cells
of the body, are not inherited, and are not passed down to our
children. Acquired mutations are always involved in causing cancer.
Germline mutations are involved in a small percentage of cases.
The formation of tumors basically results from cell growth that gets
out of control. In the human genome, there are many different types of
genes that control cell growth in a very systematic, precise way. When
these genes have an error in their DNA code, they may not work
properly, and are said to be "altered" or mutated. An
accumulation of many mutations in different genes occurring in a
specific group of cells over time is required to cause malignancy. The
different types of genes, that when mutated, can lead to the
development of cancer are described below. Remember, it takes
mutations in several of these genes for a person to develop cancer.
What specifically causes mutations to occur in these genes is largely
unknown. However, mutations can be caused by carcinogens
(environmental factors known to increase the risk of cancer). The
development of mutations is also a natural part of the aging process.
Oncogenes are altered forms of genes known as proto-oncogenes.
Proto-oncogenes are responsible for promoting cell growth. When
altered or mutated, they become oncogenes and then can promote tumor
formation or growth.
Properties of oncogenes include the following:
Mutations in proto-oncogenes are usually acquired. The
exception is that mutations in the RET proto-oncogene can be
inherited and cause a condition called multiple endocrine neoplasia
Having a mutation in just one of the two copies of
a particular proto-oncogene is enough to cause a change in cell
growth and the formation of a tumor. For this reason, oncogenes are
said to be "dominant" at the cellular level.
Tumor suppressor genes
Tumor suppressor genes are genes normally present in our cells. When
working properly, they control the processes of cell growth and cell
death (called apoptosis). Through these processes, they can also
suppress tumor development. When a tumor suppressor gene is mutated,
this can lead to tumor formation or growth.
Properties of tumor suppressor genes include the following:
Both copies of a specific tumor suppressor need to be mutated
(both members of the gene pair) in order to cause a change in cell
growth and tumor formation to occur. For this reason, tumor
suppressor genes are said to be "recessive" at the
Mutations in tumor suppressor genes are
usually acquired. The two mutations in a tumor suppressor gene pair
may occur as the result of aging and/or environmental
A mutation in a tumor suppressor gene can also be
inherited. In these cases, a mutation in one copy of the tumor
suppressor gene pair is inherited from a parent, and therefore
present in all cells of a person (germline mutation). The mutation
in the second copy of the gene (which is necessary for tumor
formation and cell growth change) is acquired and usually occurs
only in a single cell or a handful of cells. If the second
"hit" or mutation occurs in a type of cell that needs this
particular tumor suppressor gene to control cell growth, the process
of tumor formation will begin. This mechanism is also known as the
Most of the genes associated
with hereditary cancer are tumor suppressor genes. Nonetheless, most
mutations in tumor suppressor genes are not inherited.
DNA repair genes
During cell division, the DNA in a cell makes a copy or replica of
itself. During this complex process, mistakes may occur.
Mismatch-repair genes are DNA repair genes that correct these
naturally occurring spelling errors in the DNA. When these genes are
altered or mutated, however, mismatches (mistakes) in the DNA remain.
If these mistakes occur in tumor suppressor genes or proto-oncogenes,
eventually this will lead to uncontrolled cell growth and tumor
formation. There are other types of DNA repair genes that repair
errors in DNA that occur from mutagenic agents such as large doses of radiation.
Properties of DNA repair genes include the following:
Mutations in DNA repair genes can be inherited from a parent
or acquired over time as the result of aging and environmental
DNA repair genes require two mutations (both
members of the gene pair) in order for the process of tumor
formation to occur. For this reason, mismatch-repair genes are said
to be "recessive" at the cellular level.
Remember that it takes mutations in several of these genes for
cancer to develop. In most cases of cancer, all the mutations are
acquired. In inherited cancer, one mutation is passed down from the
parent, but the remainder are acquired. Because it takes more than a
single mutation to cause cancer, not all people who inherit a mutation
in a tumor suppressor gene, proto-oncogene, or DNA repair gene will
James Ford, MD, director of the Stanford Cancer Genetics Program, has always been fascinated with figuring out how genetics influences cancer. His interest is in working with families to lower their risk of familial cancer.
This video explains how genetic counselors at Stanford’s Cancer Genetics Clinic help families understand if they have a hereditary cancer syndrome and an elevated risk for colon cancer.
Clinical trials are research studies that evaluate a new medical approach, device, drug, or other treatment. As a Stanford Health Care patient, you may have access to the latest, advanced clinical trials.
Open trials refer to studies currently accepting participants. Closed trials are not currently enrolling, but may open in the future.
See the BRCA
Decision Tool which guides the management of cancer risks for
BRCA1 and BRCA2 mutation carriers.
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