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Testing Panel Familial Cancer (CGx) Panel:
This panel identifies the risk of genetic.
factors for various cancerssuch as breast
cancer, ovariancancer, colon cancer, colon
polyps,prostate cancer, melanoma, andothers
that run in a family. The test looks for inherited
genetic variations(germline mutations)
associated with an increased risk of cancer.
With knowledge of genetic riskfactors,
physicians would be able topersonalize
patient healthcare plans. Conversely, sporadic cases of breast cancer happen in patient that do not carry any mutation.
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What We Offer:
The Comprehensive Cancer Testing panel is
an assessment of 120 genes associated with
increased risk for a variety of hereditary
cancers. These associations have been
assessed by the scientific community and all
relevant research is included on reports.
Using Next Generation Sequencing
technology, variations in the genetic code can
be detected from a non-invasive buccal
swabs. These variations are assessed for
known associated risks that may allow for
preventative precautions or give insight for
future treatment. The report is
comprehensive and easy for your doctor to
interpret, allowing for them to provide the
best treatment plan possible moving forward.
Definition of cancer risk factor:
Familial cancer genetic tests provide lifetime
risk of cancer development. They cannot
state if a patient will develop cancer
for sure. But they can determine whether
an individual has a higher risk than most people.
Only some people with a gene mutation will
develop cancer. Nathanson et al. (2001) reported
lifetime breast cancer risk of 60 to 80% for
female BRCA1 mutation carriers, although
lifetime riskestimates as low as 36% had been
reported in other studies.
Method:
CGx genetic test investigates a panel of
genes (listed below) for the presence of genetic changes compared to human reference
(variants) that are linked to increased
lifetime risk of cancers. Express Gene Comprehensive Familial Cancer (Cancer) Panel
is a Laboratory Developed Tests (LDT) validated
at Express Gene Molecular Diagnostics
Laboratory, using Twist Exome 2.0 and Illumina NovaSeq6000 Next Generation Sequencing
(NGS) Platform. This test has not been cleared
or approved by the FDA.
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Limitations of Testing:
This test is designed to detect individuals with a germline pathogenic variant. Repeat expansion disease, large deletion, duplication and copy number variations, are not detectable by next generation sequencing (NGS) and require
different test methodologies. Mutations in the
upstream and downstream regulatory regions and mutations outside exons of protein-coding
genes are not investigated. Certain types of
variants, such as structural rearrangements,
inversions, translocations, variants in regions
with low complexity, regions with complex architecture, short tandem repeats, or
segmental duplications cannot be detected
by this method. Additionally, low level
mosaicism, phasing, regions with matching pseudogenes causing mapping ambiguity
cause incorrect or insufficient variant calling.
The CGx test should not be ordered on
tumor tissue.
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Genetic counseling:
Genetic counseling is recommended to explain
the results, risks, and potential pitfalls
of the CGx cancer testing panel. Genetic testing
can have potential emotional, and social,
harms. Psychological stress can arise from
learning that one has a genetic variant
that increases cancer risk, as well as from
making decisions regarding whether to
share test finding with blood relatives.
Survivor’s guilt can also occur upon learning
that one does not have a harmful variant
present in otherfamily members.
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Purpose of the CGx test:
Genes are instructions, written in DNA,
for building protein molecules. Different
people can have different versions of the
same gene. Each version has a slightly different
DNA sequence. Some of these variants affect
health, such as those gene variants
linked to increased risk ofcancers. These
cancer-related variants can run in families.
Several genes involved in manyknown inherited
cancers have beenidentified. Testing whether
someonecarries a harmful (pathogenic)variant
in one of these genes can confirm whether
a condition is,indeed, the result of an
inherited syndrome. Genetic testing is also done
to determine whether family members who
have not (yet) developed a cancer have
inherited the same variant as a family
member who is known to carry a harmful
(predisposing cancer susceptibility)variant.
More than 50 hereditary cancersyndromes
have been described. Most of these are
caused by harmful variants that are inherited
in anautosomal dominant fashion—thatis,
a single altered copy of the geneinherited
from one parent is enoughto increase a
person’s chance of developing cancer.
How Will I Benefit?
In order to treat cancer, it must be identified. The origin site and mode of cancer need to be
known as well, otherwise the battle is a shot in the dark. Certain genetic variants have been
associated with increased risks for specific cancers and can be valuable information in
preventing and treating cancer. Early diagnosis is a key factor in the success of cancer
treatment. Patients identified with hereditary cancer susceptibility can benefit from
increased surveillance and preventative steps to better manage their risk for cancer.
Knowing the specific gene involved can guide medical management and avoid
unnecessary follow up. Information obtained from&candidate gene testing may be helpful
in guiding clinical management in the future. If a pathogenic variant is identified in your
patient, close relatives (children, siblings, parents) could have as high as a 50% risk to also
be at increased risk. In some cases, screening should begin in childhood.
What is the outcome of familial cancer test results:
A. Positive Result. A positive test result
indicates a variant linked to cancer has
been identified. This knowledge provides
the patient and health care provider
an opportunity to understand and,
in some cases,manage their cancer risks.
For people who are already diagnosed with
a cancer, results of genetic testing may help
them make decisions about their treatment
and understand their risk for other cancers.
Genetic testing provides an opportunity for
family members to learn about their own
cancer risks.
B. Variation of uncertain significance (VUS).
If genetic testing shows a change that has
not been previously associated with cancer,
the person’s test result may report a VUS.
This result may be interpreted as uncertain,
which is to say that the information does not
help to clarify their risk and is typically not
considered in making health care decisions.
Some gene variants may be reclassified as
researchers learn more about variants linked
to cancer. Most often, variants that were
initially classified as variants of uncertain
significance are reclassified as being benign
(not clinically important), but sometimes a VUS
may eventually be found to be associated with
increased risks for cancer. Therefore, it is important
for the person who is tested to keep in touch with
the health care provider to ensure that they
receive updates if any new information on the
variant is learned.
C. Negative result. A negative test result
means that the laboratory did not find the
specific cancer-linked variant on list of genes
that the test was designed to detect. Therefore, patient does not have a genetic variation associated with
cancer in the genes tested by the CGx panel.
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Sources: Breast cancer genetics, PubMed:
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Familial Cancer Genetic (CGx) Testing Panel
