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Clinical Significance
NeoTYPE™
Thyroid Profile
AKT1
AKT1 mutations have been detected in patients with thyroid carcinomas. AKT1 mutations can lead to the
progression of thyroid cancers due to the constitutive activation of the cell signaling pathways. AKT inhibitors
are currently being explored as a mechanism to induce apoptosis in thyroid cancer cells. Testing for AKT1
mutations can be useful for determining sensitivity to various drugs such as PI3K/AKT inhibitors.
ALK
ALK mutations are gain-of-function mutations that have been detected in thyroid cancers such as anaplastic
thyroid carcinomas. Mutations in ALK are oncogenic and can lead to the further progression of thyroid cancers
into more aggressive forms of the the disease. Testing for ALK mutations can be useful for identifying patients
who may be sensitive to ALK inhibitors.
BRAF
BRAF mutations are common in thyroid cancers and are detected in 40-45% of papillary thyroid cancers,
20-40% of poorly differentiated carcinomas, 30-40% of anaplastic thyroid cancers and in some instances
of follicular thyroid cancers. BRAF mutations are pathogenic and testing for these mutations are critical in
determining drug sensitivity to BRAF inhibitors. Several kinase inhibitor drugs targeting patients with thyroid
cancers are currently in various phases of clinical trials.
CTNNB1
CTNNB1 mutations have been detected in thyroid cancers such as papillary thyroid cancers and anaplastic
thyroid cancers. These mutations play a role in the pathogenesis of thyroid cancers by affecting the Wnt
signaling pathways. Wnt inhibitors are currently being developed for patients with thyroid carcinomas. Testing
for CTNNB1 mutations in thyroid cancer patients can aid in determining their sensitivity to Wnt inhibitors and
other targeted therapies that are currently in clinical trials.
ERBB2
ERBB2 mutations are present in thyroid cancers. These mutations lead to the constitutive activation of the
tyrosine kinase signaling pathways, which promotes cancer growth. This gene is part of a targetable pathway
and testing for ERBB2 mutations can be useful in determining a thyroid cancer patients sensitivity to tyrosine
kinase inhibitors.
ERBB4
Oncogenic ERBB4 mutations have been detected in patients with thyroid cancer. ERBB4 is part of a targetable
pathway and testing for ERBB4 mutations can be useful in determining a thyroid cancer patients sensitivity to
tyrosine kinase inhibitors.
HRAS
HRAS mutations have been detected in 4% of thyroid cancers. The MEK inhibitor selumetinib in combination
with radioactive iodine has been shown to be effective in treating thyroid cancer patients with RAS mutations
during clinical trials. Testing for HRAS mutations may be useful in identifying thyroid cancer patients who are
sensitive to MEK inhibitors as well as other tyrosine kinase inhibitors.
KRAS
KRAS mutations have been detected in 3% of thyroid cancers. The MEK inhibitor selumetinib in combination
with radioactive iodine has been shown to be effective in treating thyroid cancer patients with RAS mutations
during clinical trials. Testing for KRAS mutations may be useful in identifying thyroid cancer patients who are
sensitive to MEK inhibitors as well as other tyrosine kinase inhibitors.
MET
Activating MET mutations have been found in a variety of thyroid cancers. MET mutations are pathogenic
and leads to increased cancer cell proliferation. MET inhibitors are currently in clinical trials for the treatment
of thyroid cancers in patients with overexpression of MET. Early studies have shown that MET inhibitors can
inhibit the growth of thyroid cancer cells. Testing for MET mutations can be useful in determining a patients
sensitivity to various tyrosine kinase inhibitors.
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NRAS
NRAS mutations have been detected in 6% of thyroid cancers. Numerous clinical trials targeting RAS mutations
in thyroid cancers are currently in development. The MEK inhibitor selumetinib in combination with radioactive
iodine has been shown to be effective in treating thyroid cancer patients with RAS mutations during clinical
trials. Testing for NRAS mutations may be useful in identifying thyroid cancer patients who are sensitive to MEK
inhibitors as well as other tyrosine kinase inhibitors.
PIK3CA
PIK3CA mutations have been identified in patient with thyroid cancers such as anaplastic thyroid cancers.
PIK3CA mutations are gain of function mutations that increases cancer activity. Testing for PIK3CA mutations
may be useful in identifying thyroid cancer patients who may be sensitive to PI3K/AKT inhibitors or other kinase
therapies.
RET
Somatic RET mutations are frequently detected in patients with thyroid cancer. RET inhibitors are currently in
development for the treatment of thyroid cancers and have shown to improve progression free-survival in various
clinical trials. Vandetanib has also been approved by the FDA to treat patients with metastatic medullary thyroid
carcinomas. Testing for RET mutations is recommended by published guidelines.
SMO
SMO is crucial in the Hedgehog pathway and is very important in oncogenesis. SMO mutations have been
detected in thyroid cancers including papillary thyroid cancers. Testing for SMO mutations can be useful as a
prognostic or therapeutic indicator. For example, itraconazole targets SMO and patients with SMO mutations
could potentially respond to this type of therapy. Clinical trials are currently being conducted on SMO mutated
patients with solid tumor cancers.
MET FISH
MET gene amplification, as detected by FISH, is one mechanism of MET overexpression and is a known
mechanism of EGFR-TKI resistance. Clinical trials have demonstrated activity of MET inhibitors against numerous
solid tumors. MET amplification is a targetable abnormality that may be useful in determining a patient’s
sensitivity to targeted therapies.
RET FISH
RET translocations occur in 10-20% of papillary thyroid carcinomas and have been seen in other thyroid cancers
as well. RET inhibitors are currently in development for the treatment of thyroid cancers and have shown to
improve progression free-survival in various clinical trials. Vandetanib has also been approved by the FDA to
treat patients with metastatic medullary thyroid carcinomas. Testing for RET translocations can be useful in
identifying thyroid caner patients who may be sensitive to targeted tyrosine kinase inhibitor therapies.
Please see our website neogenomics.com for a complete test description and printable specimen requirements. References on file.
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