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Clinical Significance
NeoTYPE™
Precision Profile for Solid Tumors
ABL1
The gene ABL1 plays a role in the control of numerous cellular processes, which may include cell proliferation
and survival. Mutations in ABL1 have been shown to be involved in the development of leukemias through the
constitutive activation of the cell signaling pathway. In addition, ABL1 mutations have also been detected in
various solid tumors such as lung, colon, melanoma and breast. Clinical trials are currently being conducted
using various kinase inhibitors targeting solid tumors with activated ABL kinases. Testing for ABL1 mutations
may be useful in determining drug sensitivity.
AKT1
AKT1 mutations plays a role in oncogensis and have been detected in varous solid tumors such as colon, lung,
ovarian and breast cancers. Testing for AKT1 mutations may be useful in identifying patients who may respond
to PI3K/AKT inhibitors or other kinase inhibitor therapies.
ALK
ALK mutations are gain-of-function mutations that have been detected in multiple solid tumor cancers.
Mutations in ALK are oncogenic and testing for ALK mutations can be useful for identifying patients who may
be sensitive to ALK inhibitors.
APC
APC mutations have been detected in numerous solid tumors, especially in colorectal cancers. APC is a tumor
suppressor gene and inactivating mutations in APC may play a role in tumor initiation and progression. Testing
for APC mutations in solid tumors may be useful in determining a patient’s diagnostic status.
ATM
The gene ATM (Ataxia Telangiectasia Mutated) plays a major role in the cell cycle checkpoint signaling
pathway. ATM mutations have been detected in numerous solid tumors such as lung, colon, gastric, ovarian
and the pancreas. Patients with mutated ATM may potentially respond to PARP inhibitors or other targeted
therapies. Testing for ATM mutations can be useful in developing therapeutic strategies.
BRAF
BRAF mutations have been detected in numerous solid tumor 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 solid tumor cancers are currently in various phases of clinical trials.
CDH1
CDH1 is mutated in a number of solid tumors, including breast, gastric, colon, thyroid and ovarian cancer.
Mutations in CDH1 can lead to the further progression of cancer through increased cell proliferation and
metastasis. Testing for CDH1 mutations can be useful in the prognostic assessment of the patient.
CDKN2A
CDKN2A is a tumor suppressor and mutations in this gene have been detected in multiple solid tumors.
Inactivating CDKN2A mutations can lead to uncontrolloed cell proliferation. Testing for CDKN2A mutations
may be useful in the diagnostic and prognostic assessment of the patient.
CSF1R
CSF1R mutations have been detected in a variety of solid tumor such as colon, lung, gastric and melanoma.
Mutations in CSF1R can lead to the constitutive activation of the cell signaling pathway. Testing for CSF1R
mutations may be useful in the prognostic assessment of the patient.
CTNNB1
CTNNB1 mutations have been detected in numerous solid tumors. These mutations play a role in the
pathogenesis of various cancers by affecting the Wnt signaling pathways. Testing for CTNNB1 mutations can
aid in determining the patients sensitivity to Wnt inhibitors and other targeted therapies that are currently in
clinical trials.
EGFR
Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor. EGFR mutations have been reported in
a number of different solid tumor cancers. Testing for EGFR mutations can be useful for screening patients who
would benefit from tyrosine kinase inhibitors.
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ERBB2
ERBB2 mutations are present in multiple solid tumor 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 patient’s sensitivity to
tyrosine kinase inhibitors.
ERBB4
Oncogenic ERBB4 mutations have been detected in multiple solid tumor cancers. ERBB4 is part of a targetable
pathway and testing for ERBB4 mutations can be useful in determining a patient’s sensitivity to tyrosine kinase
inhibitors.
FBXW7
FBXW7 mutations are found in various solid tumors. These mutations are involved in mediating the activation
of the NOTCH pathway and cause resistance to gamma-secretase inhibitors.
FGFR1
FGFR1 mutations can lead to the constitutive activation of the cell signaling pathways. These mutations have
been detected in numerous solid tumor cancers such as breast and lung. Testing for FGFR1 mutations can
be useful for identifying patients who will respond to tyrosine kinase inhibitors and FGFR small molecule
inhibitors.
FGFR2
FGFR2 mutations can lead to the constitutive activation of the cell signaling pathways. These mutations have
been detected in numerous solid tumor cancers. Testing for FGFR2 mutations can be useful for identifying
patients who will respond to tyrosine kinase inhibitors and FGFR small molecule inhibitors.
FGFR3
FGFR3 mutations can lead to the constitutive activation of the cell signaling pathways. These mutations have
been detected in numerous solid tumor cancers. Testing for FGFR3 mutations can be useful for identifying
patients who will respond to tyrosine kinase inhibitors and FGFR small molecule inhibitors.
FLT3
FLT3 mutations have been detected in solid tumors such as melanoma and lung. Testing for FLT3 mutations
may be useful in the development of targeted therapies such as FLT3 inhibitors.
GNA11
GNA11 mutations have been detected in various solid tumors such as melanomas. Mutations in GNA11 may be
useful in predicting metastases. Testing for GNA11 mutations can be useful for identifying potential targeted
therapies.
GNAQ
GNAQ mutations have been detected in various solid tumors such as melanoma. GNAQ mutations can lead
to the constitutive activation of the cell signaling pathway. Testing for GNAQ mutations can be useful in the
development of therapeutic strategies.
GNAS
Guanine nucleotide-binding protein/alpha-subunit (GNAS) gene is mutated, over-expressed and/or amplified
in a number of solid tumors. Testing for GNAS mutations can aid in targeted drug therapy decisions.
HNF1A
HNF1A mutations have been detected in different solid tumors such as the liver. HNF1A mutations are
inactivating mutations that may play a role in the progression of cancer. Testing for HNF1A mutations can
provide information that can be used to assess a patient’s cancer status.
HRAS
HRAS is highly homologous with KRAS and NRAS; all are members of the most frequently mutated family
of oncogenes. HRAS mutations have been detected in a variety of solid tumor cancers. Screening for HRAS
mutations can be useful in determining a patient’s sensitivity to tyrosine kinase inhibitors.
IDH1
IDH1 mutations have been detected in various solid tumors, particulary in gliomas. Patients with mutations in
gliomas are associated with better prognosis. Long-term survival after aggressive tumor resection has been
reported for patients with IDH1-positive astrocytomas.
JAK2
Although JAK2 mutations are more common in hematologic malignancies, they have been detected in a small
number of solid tumors. Testing for JAK2 mutations may be helpful for identifying targeted therapies such as
JAK2 inhibitors.
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JAK3
JAK3 mutations have been detected in various solid tumors. Testing for JAK3 mutations may be useful in
determining prognosis.
KDR
The gene KDR encodes VEGFR2, which is involved in mediating VEGFR-stimulated endothelial cell functions.
KDR mutations have been detected in a number of solid tumors such as lung, melanoma and colon. Testing for
KDR mutations may be useful for identifying patients that may respond to VEGF/VEGFR targeted therapies.
KIT
KIT mutations have been detected in numerous solid tumor cancers. These mutations increase the
phosphorylation of signal transduction proteins. The result is the activation of a cascade of intracellular
proteins that promote cell survival and proliferation. Testing for KIT mutations may be useful in determining a
patients sensitivity to tyrosine kinase inhibitors.
KRAS
KRAS mutations have been detected in numerous solid tumor cancers. Patients with mutant KRAS have been
shown to potentially respond to MEK inhibitors. Testing for KRAS mutations can be useful in identifying
patients who may respond to targeted therapies such as tyrosine kinase inhibitors.
MET
MET mutations have been detected in numerous solid tumor cancers. MET mutations play a role in the
pathogenesis of various cancers. Multiple antibodies against MET and small molecule MET-inhibitors are
currently in clinical trials for the treatment of various cancer types. MLH1
MLH1 mutations have been reported in a number of solid tumors, especially in colorectal cancers. Testing for
MLH1 mutations have hep in determining a patient’s risk for HNPCC.
MPL
MPL mutations have been reported in low frequencies in a number of solid tumors. Testing for MPL mutations
can be useful in identifying new treatment strategies or assessing the patient’s diagnosis.
NOTCH1
NOTCH1 mutations have been identified in multiple solid tumors and testing for these mutations may be
useful in determining sensitivity to targeted therapies. A number of NOTCH1 drug inhibitors are currently in
development to target solid tumor diseases.
NPM1
NPM1 may play a role in the regulation of a cells metatstic potential. NPM1 mutations have been detected in
low frequencies in multiple solid tumors. Testing for NPM1 mutations may be useful in assessing a patient’s
prognosis.
NRAS
NRAS is highly homologous with KRAS; both are members of the most frequently mutated family of
oncogenes. Testing for these mutations may be useful in determining tyrosine kinase inhibitor sensitivity.
PDGFRA
Platelet-derived growth factor receptor alpha (PDGFRa) gene is a member of the subfamily of type III receptor
tyrosine kinases and has been detected in patients with solid tumor cancers. Testing for PDGFRA mutations
may be useful in determining sensivity to tyrosine kinase inhibitors.
PIK3CA
PIK3CA mutations have been identified in many different solid tumor cancers. PIK3CA mutations are gain of
function mutations that increases cancer activity. Testing for PIK3CA mutations may be useful in identifying
patients who may benefit from PI3K/AKT/mTOR inhibitors or other kinase therapies.
PTEN
PTEN is one of the most commonly mutated tumor suppressors in solid tumor cancers. Clinical trials are
currently being conducted on patients with PTEN mutations. Testing for PTEN mutations may be useful in
identifying patients that are sensitive to PI3K/AKT inhibitors as well as FRAP/mTOR inhibitors.
PTPN11
PTPN11 mutations are activating mutations that can cause the proliferation of tumor cells. PTPN11 mutations
are detected in a variety of solid tumor cancers. Testing for PTPN11 mutations may be useful in the
development of targeted therapies and screening.
RB1
RB1 mutations have been detected in multiple solid tumors such as lung, colon and breast. Inactivating
RB1 mutations can play a role in tumorigenesis. Testing for RB1 mutations can be useful in the prognostic
assessment of the patient.
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RET
Somatic RET mutations are frequently detected in patients with thyroid cancer and have also been detected
in other solid tumors. 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.
SMAD4
SMAD4 mutations have been reported in a variety of solid tumors such as colon, GIST and the pancreas.
Inactivating mutations in SMAD4 can lead to the further progression of a patient’s cancer. Testing for SMAD4
mutations can be useful in a patient’s prognostic assessment.
SMARCB1
SMARCB1 mutations have been detected in multiple solid tumors, especially in soft tissue sarcomas. Testing
for SMARCB1 mutations may be useful in identifying patients that may respond to EZH2 inhibitors or other
targeted therapies.
SMO
SMO is crucial in the Hedgehog pathway and is very important in oncogenesis. SMO mutations have
been detected in multiple solid tumor 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.
SRC
The gene SRC is involved in the regulation of cellular functions such as cell growth, proliferation and migration.
Mutations in SRC may have a negative effect on a patient’s prognosis. Testing for SRC mutations may aid in the
development of targeted drug therapies since it is part of a targetable pathway.
STK11
Inactivating mutations in the gene STK11 may lead to cancer metastasis. STK11 mutations have been detected
in many solid tumors such as the cervix, lung and melanoma. Testing for STK11 mutations have be useful in the
prognostic assessment of the patient.
TP53
TP53 mutations are detected in a variety of cancers and are generally associated with a poor prognosis.
Testing for TP53 mutations can be useful in the prognostic assessment of patients with cancer.
VHL
VHL mutations have been reported in multiple solid tumors such as colon, soft tissue sarcoma and the kidneys.
VHL mutations may play a role in the metastasis of patients with renal carcinoma. Testing for VHL mutations
can aid in the diagnostic and prognostic assessemnt of the cancer patient.
Please see our website neogenomics.com for a complete test description and printable specimen requirements. References on file.
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