Liquid Biopsy
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The fact that cancerous tumors shed DNA into the
bloodstream can be used to monitor disease and
perhaps even to detect disease in people who do not
have symptoms (figure 2OA). Checking DNA pieces in
the blood plasma for oncogene or tumor suppressor
mutations is termed a liquid biopsy. The entire genome
sequence of a cancer can be deduced by overlapping
DNA pieces from the bloodstream. The simple blood test
of a liquid biopsy is much less painful and invasive than
a traditional biopsy, which samples cancer cells from
a solid tumor, such as in a breast or the liver, or from a
lining such as the skin.
The DNA detected in a liquid biopsy is called
circulating tumor DNA, or ctDNA. lt is similar to the
cell-free fetal DNA that is detected in pregnant women
(see figure 13.8). Such prenatal tests sometimes detect
cancer in an unsuspecting pregnant woman.
The first uses of liquid biopsy were in people who
already had cancer, and required monitoring lf a liquid
biopsy soon after surgery to remove a tumor does not
have ctDNA, but 2 years later does, then the cancer likely
has recurred, and may have new mutations. Liquid biopsy
is also useful for monitoring response to treatment. If
a drug is working, the level of ctDNA will decrease. lf a
cancer has become resistant to a drug, the level of ctDNA
will increase.
Using tumor DNA as a biomarker is more specific
than using a protein biomarker because a protein biomarker
may also be present on healthy cells, such as elevated
prostate-specific antigen. Circulating tumor DNA can also be
collected from urine (bladder cancer), sputum (lung cancer),
and feces (colorectal cancer). A liquid biopsy is particularly
useful when tissue is difficult to obtain or not enough cells
are sampled, or when cancer has spread and the initial site is
unknown.
More controversial than detection of ctDNA for people
who already have cancer is its use to screen high-risk
populations, such as people who smoke (for lung cancer) or
people with family histories of specific cancers. A finding of
ctDNA in a person vyho does not have cancer symptoms can
warn the individual to seek additional types of tests that might
diagnose cancer very early.
Liquid biopsy might be used someday on everyone\’ to
detect cancers that are entirely unsuspected. For example,
ovarian cancer is sometimes diagnosed at a very late stage
because the symptoms of bloating and fatigue are vague and
common, and may be attributed to other factors, such as a change
in diet or exercise routine. The danger of using liquid biopsy on
people of average risk, however, is a false positive finding-an
oncogene or tumor suppressor variant that doesn\’t cause cancer
in everyone, due to effects of other genes. Liquid biopsies are
being done in clinical trials on thousands of healthy people
at low or average risk of cancer to assess the predictive value of
the technology.
Questions for Discussion
1. What would you want to know before you have a liquid
biopsy?
2. What are the advantages and possible disadvantages of a
liquid biopsy?
3. Explain why the results of a liquid biopsy would likely
change as a cancer is monitored over many years.
4. When in the course of checking someone for cancer do you
think a liquid biopsy should be offered?
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FigUfe 2OA liquia biopsy. Detecting tumor cell DNA in the blood is
a less invasive way to monitor cancer recurrence than a traditional surgical
biopsy. Source: Nationol Humon Genome Reseorch lnstitute.
Chapter 20 Concer Genetics ond Genomics 391
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