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Includes, CPT Codes, Descriptions, and Disease/Specialty cross reference.
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Tests By Type
|
ref# |
Test Type |
Test Name |
CPT code |
Includes |
Description |
Clinical Significance |
Normal Ranges |
Specimen |
|
6 |
PCR |
B Cell / IgH (JH) Lambda Light Chain |
83890 (1), 83894 (1), 83912 (1), 83898(1) |
Extraction, Amplification/Primers, Gel
Electrophoresis & Interpretation |
B Cell clonality -- Immunoglobulin Lambda Light
Chain (l) Gene rearrangement Assay used to
identify clonal B-cell populations highly
suggestive of B-cell malignancies. May also be
used to diagnose leukemias and lymphomas, and
for prognosis and treatment selection.
Determination of lineage, detection of residual
disease and monitoring disease recurrence are
also possible. |
clonality does not equal malignancy but supports
lympho profiferative disorder |
polyclonal |
Peripheral Blood, Bone Marrow, archival tissue |
|
3 |
PCR |
B Cell / IgH (JH) Heavy Chain |
83890 (1), 83898 (3), 83894 (1), 83912 (1) |
Extraction, Amplification/Primers, Gel
Electrophoresis & Interpretation |
B Cell clonality -- Immunoglobulin Heavy Chain
Gene Rearrangement (IGH) Assay used to identify
clonal B-cell populations highly suggestive of
B-cell malignancies. May also be used to
diagnose leukemias and lymphomas, and for
prognosis and treatment selection. Determination
of lineage, detection of residual disease and
monitoring disease recurrence are also possible. |
|
polyclonal |
Peripheral Blood, Bone Marrow, archival |
|
5 |
PCR |
B Cell / IgH (JH) Kappa Light Chain |
83890 (1), 838898(1), 83894 (1), 83912 (1) |
Extraction, Amplification/Primers, Gel
Electrophoresis & Interpretation |
B Cell clonality -- Immunoglobulin Kappa Light
Chain (k) Gene rearrangement. Assay used to
identify clonal B-cell populations highly
suggestive of B-cell malignancies. May also be
used to diagnose leukemias and lymphomas, and
for prognosis and treatment selection.
Determination of lineage, detection of residual
disease and monitoring disease recurrence are
also possible. |
|
|
Peripheral Blood, Bone Marrow, archival |
|
8 |
PCR |
BCL1 t(11;14) |
83890 (1), 83898 (2), 83894 (1), 83912 (1) |
Extraction, Amplification/Primers, Gel
Electrophoresis & Interpretation |
BCL1/JH t(11;14) Translocation Assays
t(11;14)(q13;q32) This PCR assay is used to
identify gene rearrangements usually associated
with mantle cell lymphoma. This translocation
can also be found in B-promyelocytic leukemia
(10-20%), plasma cell leukemia, splenic lymphoma
with villous lymphocytes, chronic lymphocytic
leukemia (2-5%), and in multiple myeloma
(20-25%). May be used diagnostically and
prognostically as well as for treatment
selection and monitoring disease recurrence. |
The chromosomal translocation t(11;14) is
strongly associated with and occurs in
approximately 95 percent of mantle cell
lymphomas, also known as lymphocytic lymphoma of
intermediate differentiation (IDL) and
centrocytic lymphoma. This chromosomal
translocation is characterized by an aberrant
gene rearrangement between the IgH joining
region (JH) on chromosome 14 and the bcl-1 locus
on chromosome 11. Forty to 50 percent of
breakpoints within the bcl-1 locus occur at the
so-called major translocation cluster (MTC) and
can be detected by PCR methodology. However,
some breakpoints occur at distant loci and will
not be identified by this particular test.
Therefore, a negative result does not completely
exclude the presence of a bcl-1/JH gene
rearrangement in the sample. In addition, a
small subset of splenic marginal zone lymphomas
reportedly have this rearrangement. Results of
this test must always be interpreted in the
context of morphologic and other relevant data
and should not be used alone for a diagnosis of
malignancy. |
negative |
Peripheral Blood, Bone Marrow, archival tissue,
lymph node |
|
11 |
PCR |
BCL2 t(14;18) |
83890 (1), 83898 (4), 83894 (1), 83912 (1) |
Extraction, Amplification/Primers (Major), Gel
Electrophoresis & Interpretation |
BCL2/JH t(14;18) Translocation Assays
t(14;18)(q32;q21) This translocation is found in
80-90% of follicular lymphomas and 30% of
diffuse large cell lymphomas. This PCR assay is
used in the diagnostic evaluation and monitoring
of follicular lymphomas and other B cell
lymphomas. It can be used to distinguish
lymphoma from benign lymphoid hyperplasia and to
Distinguish follicular lymphoma from other B
cell lymphomas that may have a similar
appearance. This assay can also be used to
determine the prognosis for patients with B cell
lymphomas and for monitoring B cell lymphoma
patients for disease recurrence. |
The chromosomal translocation t(14;18) is
present in approximately 90 percent of
follicular lymphomas and in a significant
minority (10-30%) of diffuse large-cell
lymphomas of B-cell lineage. It is characterized
by an aberrant gene rearrangement between the
IgH joining region (JH) on chromosome 14 and the
bcl-2 protooncogene on chromosome 18. Moreover,
there are two primary breakpoint loci in the
bcl-2 region, accounting for about 70 percent of
translocations: The more common major breakpoint
region (mbr/JH, 60%) ; the less frequent minor
cluster region (mcr/JH, 10%). |
negative |
|
|
18 |
PCR |
Chimerism (post-transplant ) |
83890 (3), 83901 (48), 83894 (3), 83912 (1) |
Extraction, Amplification / Primer, Gel
Electrophoresis, & Interpretation |
After a bone marrow transplant, PCR for
chimerism can be used to assess the proportion
of donor cells versus recipient cells in same
sex trasplants using predetermined allele
testing to evaluate engraftment, detect the
presence of clonal neoplasms and determine
disease recurrence. Specimens required – donor,
recipient pre-transplant and post-transplant |
Bone Marrow typing post transplant- Transplant
Evaluation |
recepient allelotype |
|
|
26 |
PCR |
Cystic Fibrosis – PCR – 33 Mutation Panel |
83890 (1), 83894 (1), 83896 (32), 83912 (1),
83901 (4) |
Extraction, Multiplex, Gel Electrophoresis, &
Interpretation |
Cystic fibrosis (CF) is an autosomal recessive
disorder caused by mutations in the CFTR gene
that encodes a chloride channel protein. This is
the most common hereditary disease in
Caucasians. A 33 mutation panel using
oligonucleotide probe technology is used |
Cystic fibrosis (CF) is a common inherited
disease in Caucasians affecting approximately
1:3,000 individuals. The incidence in other
ethnic groups varies from 1:15,000 for African
Americans to 1:90,000 in Asians. In 1989, the
gene for cystic fibrosis was discovered. The
protein determined from the DNA sequence was
found to be a chloride channel regulator (cystic
fibrosis transmembrane conductance regulator or
CFTR). More than 1,000 mutations have been found
in the cystic fibrosis gene; however, most of
these mutations are very rare. The most common
mutation is a deletion of phenylalanine at
position 508 of the CFTR protein (F508del). This
accounts for about 70 percent of CF alleles in
European Caucasians and about 50 percent of
affected Caucasians have two copies of this gene
mutation. |
Negative: The sample is negative for the
mutations screened, including the 25 CF
mutations recommended by the American College of
Medical Genetics. |
Amnionic Fluid, Peripheral Blood |
|
33 |
PCR |
DNA Sequencing |
83890 (1), 83894 (1), 83898 (1), 83912(1) |
Extraction, Gel Electrophoresis, Amplification /
Primer, Sequencing, & Interpretation |
Mutation screening for a variety of disease.
Sequencing dependent upon disease and mutation. |
|
|
|
|
40 |
PCR |
FLT3 mutation assay |
83890 (1), 83901 (2), 83892 (1), 83894 (1),
83912 (1) |
Extraction, Multiplex, Gel Electrophoresis,
Enzyamatic Digestion & Interpretation |
Identifies common FLT3 mutations, common in
acute myelogenous leukemia (AML) has been
diagnosed. |
The principal use for the FLT3 internal tandem
duplication assay is to detect the presence of
mutations in this gene in a patient sample in
which acute myelogenous leukemia (AML) has been
diagnosed. As currently configured, this assay
is intended to serve as a qualitative test and
should not be used to detect minimal residual
disease. Mutations in the FLT3 gene have been
described in 17-30 percent of acute myelogenous
leukemia (AML) cases. The majority of these
mutations occur as internal tandem duplications
(ITD) in the juxtamembrane domain-coding
sequence of the FLT3 gene. Mutations in this
region result in constitutive activation of the
FLT3 protein. FLT3 gene mutations have been
found in all AML FAB sub-types. These mutations
have also been observed in some cases of
myelodysplastic syndrome (MDS). The presence of
FLT3 mutations has both prognostic and
therapeutic implications. The detection of FLT3
mutations is therefore an important parameter to
consider in the management of AML. |
The FLT3 internal tandem duplication assay
detects the presence of ITD mutations by
polymerase chain reaction (PCR). PCR products
are detected by capillary electrophoresis (CE).
DNA from a sample known to contain a FLT3 ITD
mutation is utilized as a positive control.
Patient samples containing only the wild-type
allele exhibit a single CE peak at 329 bp and
are scored negative for the mutation. Patient
samples containing an allele with an ITD
mutation exhibit CE peaks greater than 329 bp
and are scored positive. |
|
|
42 |
PCR |
Hemoglobin A, C, S |
83890 (1), 83898 (1), 83894 (2), 83912 (1),
83892(2) |
Extraction, Amplification/Primer, nucleic acid
probe & Interpretation |
Used to rule out sickle cell trait or disease in
a fetus at risk. |
Approximately 400 mutant hemoglobins are now
known, some of which may cause serious clinical
effects. This is especially true in the
homozygous state or in combination with another
abnormal hemoglobin. The abnormalities of
hemoglobin synthesis can be divided into three
groups: • Production of an abnormal protein
molecule (e.g., sickle-cell anemia) • Reduction
in the amount of normal protein synthesis (e.g.,
thalassemia) • Developmental anomalies (e.g.,
hereditary persistency of fetal hemoglobin [HPFH]).
Differential diagnosis can lead to improved
treatment of the patient, as well as genetic
counseling. Sickle cell anemia is an inherited
disease characterized by the presence of
hemoglobin S, which occurs in either the
homozygous (S/S-sickle cell anemia), or
heterozygous (A/S-sickle cell trait) form. In a
normal adult, at least 95 percent of the
hemoglobin present is hemoglobin A. Hemoglobin
S, inherited in the homozygous (S/S) form, is
often fatal before adolescence. However, with
early detection and treatment, survival into the
adult years is possible. The most obvious
clinical symptoms are severe hemolytic anemia
with concurrent effects on various organ systems
(i.e., spleen, kidneys, lungs, central nervous
system, bones). If inherited in the heterozygous
(A/S) form, it is usually asymptomatic except
under certain circumstances of reduced oxygen
tension. |
|
|
|
45 |
PCR |
Hypercoagulability Panel |
83890 (1), 83896 (3), 83898 (3), 83912 (1) |
Factor V (Leiden), Factor II (Prothrombin),
MTHFR, & Interpretation |
Includes Factor V(Leiden) [R506Q], Prothrombin
20210 (G20210A), and MTHFR (C677T) |
Factor V Leiden testing is beneficial for
presymptomatic evaluation of at-risk individuals
and for individuals with a history of DVT
because anticoagulant therapy can be initiated.
In addition, those individuals that are positive
for the factor V Leiden mutation can be advised
of the risk of thrombotic events for other
family members. A single point mutation in the
factor V gene (at nucleotide position 1,691,
guanine-to-adenine substitution) predicts the
synthesis of a factor V molecule with arginine
at amino acid residue 506 versus glutamine
(wild-type). This R506Q substitution prevents a
peptide bond in the coagulation molecule from
being cleaved by activated protein C (APC).
During normal homeostasis, APC limits clot
formation by proteolytic inactivation of factor
Va and VIIIa. Resistance to this activity
increases the risk of deep-vein thrombosis. The
allelic frequency of the mutation may approach
five percent and is at least 10 times higher
than all other known genetic risk factors for
thrombosis (protein C, protein S, and
antithrombin deficiency). The factor V Leiden
mutation accounts for greater than 90 percent of
cases with APC-resistance. Inherited thrombosis
due to APC resistance is considered an autosomal
dominant disease. Heterozygote carriers of the
factor V Leiden polymorphism have an increased
risk of thrombosis of 5- to 10-fold, while
homozygotes have an 50- to 100-fold increased
risk. Estimated penetrance for homozygotes is
close to 80 percent, with a reduced penetrance
for heterozygotes (approximately 12-20 percent).
Mutations in other genes or other mutations in
the factor V gene that may cause APC resistance
and venous thrombosis are not ruled out. It is
also, however, becoming increasingly apparent
that additional genetic or non-genetic risk
factors are important in precipitating
thrombotic events. Pregnancy, the use of oral
contraceptives, and immobilization are
non-genetic risk factors that are associated
with increased risk of thrombosis in the APC-resistant
patient. Many patients with recurrent episodes
of thrombosis have more than one genetic risk
factor, such as concomitant factor II (prothrombin)
G20210A mutation, protein C deficiency, or
homocystinemia. APC-R is associated with
recurrent miscarriage (loss of three or more
consecutive pregnancies) in the second trimester
of pregnancy, accounting for 20 percent of cases
in one study. The factor II (prothrombin)
mutation is the second most common genetic
defect for inherited thrombosis, with factor V
Leiden being the most common. The genetic
variant is found in the 3´ untranslated region
of the factor II (prothrombin) gene. This
variant, a G-to-A substitution at nucleotide
position 20210 (G20210A) is associated with
increased prothrombin levels. A single copy of
this variant (heterozygote) increases the risk
of venous thrombosis from between three to 11
percent. Two copies of the 20210A allele
(homozygous) further increases this risk. In
Caucasians, the prevalence of factor II G20210A
heterozygotes is one to six percent, whereas in
non-Caucasian populations it is very rare or
absent. The 20210A allele is associated with an
increased risk for thrombosis. The G20210A
prothrombin mutation in a homozygous state
further increases the risk for developing
thrombosis. The G20210A mutation causes elevated
plasma prothrombin levels, which in turn
increase the risk for a thrombotic event.
Increased levels of prothrombin also pose a risk
for myocardial infarction if other risk factors
such as smoking, hypertension, diabetes
mellitus, or obesity exist. The 20210A allele of
the prothrombin gene may be coinherited with the
factor V Leiden mutation. The combined
heterozygosity for the two defects leads to an
earlier onset and a more severe thrombotic
episode than single-gene defects. The
prothrombin mutation assay is indicated for
patients with thrombosis, pregnancy
complications due to abruptio placenta and fetal
growth retardation, or those with significant
family histories of thrombosis. The clinical
scenario should be considered carefully, since
additional factors, both genetic and non
genetic, are important in the development of
thrombosis. This assay is specific for the
prothrombin G20210A mutation. Other mutations
within the prothrombin gene or mutations in
other genes that cause elevated prothrombin and
hereditary forms of venous thrombosis will not
be detected; consequently, such mutations cannot
be ruled out. Results are reported as homozygous
(two copies for the mutation), heterozygous (one
copy of the mutant gene and one copy of the
normal gene), or negative (two copies of the
normal gene). This assay may be used to confirm
the diagnosis of inherited thrombophilia in
symptomatic patients or to provide family
members information on their inherited risk of
prothrombin-related thrombosis. |
• Negative: The patient is negative for Factor V
Leiden, R506Q polymorphism. • Heterozygous: The
patient is heterozygous for Factor V Leiden,
R506Q polymorphism. This is associated with
activated protein C resistance and an increased
risk for venous thrombosis. • Homozygous: The
patient is homozygous for Factor V Leiden, R506Q
polymorphism. This is associated with activated
protein C resistance and an increased risk for
venous thrombosis. |
|
|
78 |
PCR |
JAK2 V617F Activating Mututation |
83890 (1), 83901 (2), 83894 (1), 83892 (1)
,83912 (1) |
Extraction, Multiplex, Restriction Digest, Gel
Electrophoresis, & Interpretation |
Polycythemia vera and other myeloproliferative
disorders harbor activating mutations in JAK2.
Testing is performed on peripheral blood or bone
marrow in patients with chronic
myeloproliferative disorders, such as
polycythemia vera. |
JAK2 gene (JAK2-V617F) is found in the great
majority of patients with PV, but also in the
minority of patients with ET and other MPDs. |
|
|
|
69 |
PCR |
T Cell Receptor- Beta |
83890 (1), 83901 (4), 83894 (1), 83912 (1) |
Extraction, Multiplex, Gel Electrophoresis, &
Interpretation |
T Cell Receptor Beta Chain Gene Rearrangement
Assays The TCRβ gene locus is located on
chromosome 7 (7q35). This PCR assay is used to
identify clonal T-cell populations highly
suggestive of T-cell malignancies. Determination
of lineage, detection of residual disease and
monitoring disease recurrence are also possible. |
|
Negative: A monoclonal T-cell population is not
detected; Positive: A monoclonal T-cell
population is detected |
|
|
70 |
PCR |
T Cell Receptor- Delta |
83890 (1), 83901 (1), 83894 (1), 83912 (1) |
Extraction, Multiplex, Gel Electrophoresis, &
Interpretation |
T Cell Receptor Delta Chain Gene Rearrangement
Assays The TCRδ gene locus is located on
chromosome 14 (14q11.2). This PCR assay is used
to identify clonal T-cell populations highly
suggestive of T-cell malignancies. Determination
of lineage, detection of residual disease and
monitoring disease recurrence are also possible. |
The diagnosis of non-Hodgkin's lymphoma is
usually based on morphologic features and
confirmatory immunophenotypic data. However, in
a subset of cases, a definitive diagnosis cannot
be established using this approach alone. The
molecular genetic evaluation of lymphocytic
proliferations for evidence of immunoglobulin
(Ig) and T-cell receptor gene rearrangements is
useful for establishing clonality in this
situation. Although a few exceptions do exist,
monoclonality generally correlates with
neoplasia and polyclonality is found in benign
reactive conditions. As such, this molecular
genetic information can be used as an adjunct
marker documenting the reactive or neoplastic
nature of a particular process in the
appropriate setting. |
Negative: A monoclonal T-cell population is not
detected; Positive: A monoclonal T-cell
population is detected |
|
|
71 |
PCR |
T Cell Receptor- Gamma |
83890 (1), 83901 (2), 83894 (1), 83912 (1) |
Extraction, Multiplex, Gel Electrophoresis, &
Interpretation |
T Cell Receptor Gamma Chain Gene Rearrangement
Assays The TCRγ chain locus is located on
chromosome 7 (7p15-p14). This PCR assay is used
to identify clonal T-cell populations highly
suggestive of T-cell malignancies. Determination
of lineage, detection of residual disease and
monitoring disease recurrence are also possible. |
The diagnosis of non-Hodgkin's lymphoma is
usually based on morphologic features and
confirmatory immunophenotypic data. However, in
a subset of cases, a definitive diagnosis cannot
be established using this approach alone. The
molecular genetic evaluation of lymphocytic
proliferations for evidence of immunoglobulin
(Ig) and T-cell receptor gene rearrangements is
useful for establishing clonality in this
situation. Although a few exceptions do exist,
monoclonality generally correlates with
neoplasia and polyclonality is found in benign
reactive conditions. As such, this molecular
genetic information can be used as an adjunct
marker documenting the reactive or neoplastic
nature of a particular process in the
appropriate setting. |
Negative: A monoclonal T-cell population is not
detected; Positive: A monoclonal T-cell
population is detected |
|
|
79 |
PCR |
Y Chromosome Deletions / Azospermia |
83890 (1), 83901 (5), 83894 (1), 83912 (1) |
Extraction, Multiplex, Gel Electrophoresis, &
Interpretation |
Y chromosome deletions are primarily involved in
the etiology of male infertility. |
|
|
|
|
44 |
PCR, IHC |
Hereditary Nonpolyposis Screen for Colorectal
Cancer (HNPCC) |
83890 (2), 83901 (2), 83894(2), 88342 (3), 83912
(1) |
Extraction, Amplification/Primer, Gel
Electrophoresis, Immunocytochemistry, &
Interpretation |
Samples from a tumor specimen and normal tissue
are amplified by PCR for the five microsatellite
markers: BAT 25, BAT 26, D2S123, D5S346, and
D17S250. Fluorescently labeled products are
detected and sized by capillary electrophoresis.
Patterns of normal and tumor genotypes are
compared for each marker and scored as stable or
unstable. Microsatellite instability-high in a
tumor indicates significant levels of
microsatellite instability. MSI-high occurs in
approximately 90% of colorectal cancers from
individuals with hereditary nonpolyposis
colorectal cancer (HNPCC) and in 10-15% of
sporadic colon cancer. MSI-low or MSI-stable
indicates a lack of significant microsatellite
instability in a tumor. NOTE: both normal
(non-tumor) and tumor tissue are required to
accurately identify MSI. Specimens required:
Must send tumor and normal tissue samples from
patient. |
Microsatellite instability-high in a tumor
indicates significant levels of microsatellite
instability. MSI-high occurs in approximately
90% of colorectal cancers from individuals with
hereditary nonpolyposis colorectal cancer
(HNPCC) and in 10-15% of sporadic colon cancer.
|
|
|
|
36 |
Real Time PCR |
Factor II / Prothrombin (G20210A) |
83890 (1), 83898 (1), 83896 (1), 83912 (1) |
Extraction, Amplification/Primer, Nucleic Acid
Probe, & Interpretation |
Factor II (Prothrombin) G20210A. This mutation
is present in 1-2% of the general population and
it is involved in venous thromboembolism, which
is the third most common cardiovascular disease. |
|
|
|
|
37 |
Real Time PCR |
Factor V Leiden (R506Q) |
83890 (1), 83898 (1), 83896 (1), 83912 (1) |
Extraction, Amplification/Primer, Nucleic Acid
Probe, & Interpretation |
Factor V Leiden mutation (R506Q) This mutation
is present in about 5% of Caucasians and
accounts for 85% to 95% of APC resistance cases.
Associated with venous thrombosis. |
Factor V Leiden testing is beneficial for
presymptomatic evaluation of at-risk individuals
and for individuals with a history of DVT
because anticoagulant therapy can be initiated.
In addition, those individuals that are positive
for the factor V Leiden mutation can be advised
of the risk of thrombotic events for other
family members. A single point mutation in the
factor V gene (at nucleotide position 1,691,
guanine-to-adenine substitution) predicts the
synthesis of a factor V molecule with arginine
at amino acid residue 506 versus glutamine
(wild-type). This R506Q substitution prevents a
peptide bond in the coagulation molecule from
being cleaved by activated protein C (APC).
During normal homeostasis, APC limits clot
formation by proteolytic inactivation of factor
Va and VIIIa. Resistance to this activity
increases the risk of deep-vein thrombosis. The
allelic frequency of the mutation may approach
five percent and is at least 10 times higher
than all other known genetic risk factors for
thrombosis (protein C, protein S, and
antithrombin deficiency). The factor V Leiden
mutation accounts for greater than 90 percent of
cases with APC-resistance. Inherited thrombosis
due to APC resistance is considered an autosomal
dominant disease. Heterozygote carriers of the
factor V Leiden polymorphism have an increased
risk of thrombosis of 5- to 10-fold, while
homozygotes have an 50- to 100-fold increased
risk. Estimated penetrance for homozygotes is
close to 80 percent, with a reduced penetrance
for heterozygotes (approximately 12-20 percent).
Mutations in other genes or other mutations in
the factor V gene that may cause APC resistance
and venous thrombosis are not ruled out. It is
also, however, becoming increasingly apparent
that additional genetic or non-genetic risk
factors are important in precipitating
thrombotic events. Pregnancy, the use of oral
contraceptives, and immobilization are
non-genetic risk factors that are associated
with increased risk of thrombosis in the APC-resistant
patient. Many patients with recurrent episodes
of thrombosis have more than one genetic risk
factor, such as concomitant factor II (prothrombin)
G20210A mutation, protein C deficiency, or
homocystinemia. APC-R is associated with
recurrent miscarriage (loss of three or more
consecutive pregnancies) in the second trimester
of pregnancy, accounting for 20 percent of cases
in one study. The factor II (prothrombin)
mutation is the second most common genetic
defect for inherited thrombosis, with factor V
Leiden being the most common. The genetic
variant is found in the 3´ untranslated region
of the factor II (prothrombin) gene. This
variant, a G-to-A substitution at nucleotide
position 20210 (G20210A) is associated with
increased prothrombin levels. A single copy of
this variant (heterozygote) increases the risk
of venous thrombosis from between three to 11
percent. Two copies of the 20210A allele
(homozygous) further increases this risk. In
Caucasians, the prevalence of factor II G20210A
heterozygotes is one to six percent, whereas in
non-Caucasian populations it is very rare or
absent. The 20210A allele is associated with an
increased risk for thrombosis. The G20210A
prothrombin mutation in a homozygous state
further increases the risk for developing
thrombosis. The G20210A mutation causes elevated
plasma prothrombin levels, which in turn
increase the risk for a thrombotic event.
Increased levels of prothrombin also pose a risk
for myocardial infarction if other risk factors
such as smoking, hypertension, diabetes
mellitus, or obesity exist. The 20210A allele of
the prothrombin gene may be coinherited with the
factor V Leiden mutation. The combined
heterozygosity for the two defects leads to an
earlier onset and a more severe thrombotic
episode than single-gene defects. The
prothrombin mutation assay is indicated for
patients with thrombosis, pregnancy
complications due to abruptio placenta and fetal
growth retardation, or those with significant
family histories of thrombosis. The clinical
scenario should be considered carefully, since
additional factors, both genetic and non
genetic, are important in the development of
thrombosis. This assay is specific for the
prothrombin G20210A mutation. Other mutations
within the prothrombin gene or mutations in
other genes that cause elevated prothrombin and
hereditary forms of venous thrombosis will not
be detected; consequently, such mutations cannot
be ruled out. Results are reported as homozygous
(two copies for the mutation), heterozygous (one
copy of the mutant gene and one copy of the
normal gene), or negative (two copies of the
normal gene). This assay may be used to confirm
the diagnosis of inherited thrombophilia in
symptomatic patients or to provide family
members information on their inherited risk of
prothrombin-related thrombosis. |
|
|
|
41 |
Real Time PCR |
Hemochromatosis (H63D, C282Y,S65C) |
83890 (1), 83898 (3), 83896 (3) , 83912 (1) |
Extraction, Amplification/Primer, Nucleic Acid
Probes, & Interpretation |
Hereditary hemochromatosis is caused by
mutations in HFE. Three mutations are linked to
the disease: C282Y, H63D, and S65C. The C282Y
mutation is seen in approximately 95% of
hemochromatosis patients. The H63D and S65C
mutations are linked to milder forms of the
disease. |
Hereditary hemochromatosis is one of the most
common genetic diseases in individuals from
Northern European descent, affecting 1 in every
200-400 individuals. It is an autosomal
recessive disorder of iron metabolism and is
expressed more severely in males than in
females. In hereditary hemochromatosis, iron
accumulation in a variety of organs leads to
organ failure. Several complications of iron
accumulation are cirrhosis, diabetes, and
cardiomyopathy. Symptomatic disease typically
presents after the age of 50 and is most common
in Caucasian males. In a Utah-based study, the
male-to-female ratio was 2 to 1. Signs and
symptoms are a result of progressive tissue iron
accumulation. Early symptoms may be vague and
easily overlooked. By the time specific symptoms
and signs are identifiable, there is typically
marked iron accumulation, usually greater than
10,000 µg/g dry weight in liver biopsy
specimens. In those patients who have hepatic
cirrhosis, concentrations are often greater than
20,000 µg/g dry weight. Young asymptomatic
patients will have significantly lower tissue
iron levels, but will still be abnormal. The
lower incidence of this disorder in females is
partially attributable to the protective effects
of menstrual blood loss and pregnancy in
premenopausal women. The most common mutation
described is a G to A transition at nucleotide
845, which substitutes a tyrosine for a cysteine
at amino acid position 282. The C282Y mutation
is responsible for up to 90 percent of disease
in hemochromatosis patients. One out of twelve
individuals carry this mutation, although
significant symptoms are not usually present in
heterozygotes. Penetrance of C282Y homozygosity
continues to be intensely debated. Current
studies estimate penetrance as 80 percent for
men and 35 percent for women over 40. Additional
studies estimate much lower penetrance for liver
disease (~1%). In women over 40, penetrance is
80 percent for iron overload with 13 percent
showing other symptoms. Two other mutations
(H63D and S65C) have been described in some
cases of hemochromatosis. The H63D mutation is a
C to G transversion at nucleotide position 187,
which substitutes an aspartic acid for histadine.
The S65C mutation is an A to T substitution at
nucleotide position 193, resulting in cysteine
replacing serine. Compound heterozygotes for
C282Y/H63D have a relative penetrance estimated
as 0.5 to 1.5 percent, indicating that less than
2 percent have clinical symptoms of hereditary
hemochromatosis. Studies indicate that S65C has
a modest effect on iron metabolism. The mutation
appears to be in a region implicated in binding
the transferrin receptor to the HFE protein.
While the C282Y mutation may be associated with
a severe phenotype, the H63D and S65C mutations
are associated with a milder phenotype. Compound
heterozygotes for C282Y/H63D and C282Y/S65C and
homozygotes for the H63D have been described in
some individuals showing mild symptoms, although
most have no detectable symptoms of
hemochromatosis. H63D has an allele frequency of
approximately 16 percent in the general
population, while S65C has an allele frequency
of 1.5 percent. The allele frequency of S65C in
affected populations is uncertain. |
|
|
|
59 |
Real Time PCR |
MTHFR - Methylenetetrahydrofolate Reductase
(C677T) |
83890 (1), 83898 (1), 83896 (1), 83912 (1) |
Extraction, Amplification/Primer, Nucleic Acid
Probe, & Interpretation |
MTHFR (5,10-methylenetetrahydrofolate reductase
(NADPH) (C677T). Reduced MTHFR leads to elevated
plasma homocysteine levels and has been reported
in patients with coronary and peripheral artery
disease and correlates with reduced enzyme
activity in both homozygous and heterozygous
mutations. |
A common mutation (nucleotide 677 C-->T) in the
methylenetetrahydrofolate reductase (MTHFR) gene
contributes to a mild rise in plasma
homocysteine levels and increase the incidence
of coronary artery disease and
hypercoagulability. |
|
|
|
117 |
RT-PCR (QPCR) |
AML / ETO t(8;21 ) |
83890 (1), 83898 (1), 83896 (1), 83902 (1),
83912 (1) |
Extraction, Amplification/Primer, Nucleic Acid
Probes, Reverse Transcription, & Interpretation |
The AML1/ETO translocation probe is designed to
detect the juxtaposition of the AML1 gene locus
on chromosome 21q22 with the ETO gene locus on
chromosome. The 8;21 translocation event
produces a fusion of the two genes on the
derivative 8 chromosome that results in the
novel chimeric gene, AML1/ETO. Variant
translocations involving chromosomes 8 and 21
also exist and can be missed in an unusual or
complex karyotype. Quantitative RT-PCR is done
to assess transcript levels of AML/ETO. |
The AML1-ETO fusion transcript is present in
some cases of the FAB-M2 subtype of acute
myelogenous leukemia (AML). This transcript
results from a translocation involving the AML1
gene on chromosome 21 and the ETO (or MTG8) gene
on chromosome 8. The t(8;21) is found in nearly
7 percent of de novo AML and is more common in
younger patients. It is found in 20-40 percent
of AML-M2 subtype cases. It is clinically
important to assess leukemia cases for the
presence of the t(8;21), because it is
associated with a relatively good prognosis and
good response to certain therapeutic agents.
This test is useful for the diagnosis of a
subset of acute myelogenous leukemia, called
AML-M2. The presence of the t(8;21) transcript
defines a subgroup of AMLs with a favorable
prognosis. |
|
Peripheral Blood, Bone Marrow |
|
14 |
RT-PCR (QPCR) |
BCR / ABL t(9;22) |
83890 (1), 83898 (1), 83896 (1), 83902 (1),
83912 (1) |
Extraction, Amplification/Primer, Nucleic Acid
Probes, Reverse Transcription, & Interpretation |
BCR/ABL Gene Rearrangement t(9;22) quantitative
real time RT-PCR(QPCR). The BCR/ABL
translocation is found in 90-95% of all chronic
myelogenous leukemias (CML) patients and 30% of
acute lymphocytic leukemias (ALL) cases. The
presence of the Philadelphia chromosome can be
used to diagnose CML and ALL and to assess the
prognosis. It may also be used to predict
disease remission and relapse and to monitor
therapeutic response to Gleevec. |
Generally, the bcr/abl fusion transcript is
found in chronic myelogenous leukemia (CML) and
a distinct subset of acute lymphoblastic
leukemia (ALL). |
|
Peripheral Blood, Bone Marrow |
|
22 |
RT-PCR (QPCR) |
Chromosome 16 Inversion |
83890 (1), 83896 (1), 83898 (1), 83902 (1),
83912 (1) |
Extraction, Multiplex, Amplification / Primer,
Reverse Transcription & Interpretation |
Inv (16), AML-M4 CBFB/MYH11 quantitative real
time RT-PCR. The inversion of chromosome 16 is
found in the AML-M4 subtype of acute myelocytic
leukemias (AML). It represents 7-10% of all new
AML cases and more than 90% of the M4 subtype.
This test may be used as a diagnostic tool,
minimum residual disease testing, to predict
disease remission or detect relapse. |
The principal use for this test is to detect the
presence of CBFB-MYH11 fusion transcripts in
patients with AML-M4Eo or an indication of
inv(16). This test is not intended to detect
minimal residual disease. |
negative |
|
|
64 |
RT-PCR (QPCR) |
PML / RARA t(15;17) |
83890 (1), 83896 (1), 83898 (1), 83902 (1),
83912 (1) |
Extraction, Multiplex, Amplification / Primer,
Reverse Transcription & Interpretation |
PML-RARA gene rearrangement t(15;17)
quantitative real time RT-PCR, AML-M4. The
PML-RARA translocation is found in acute
promyelocytic leukemias (APL), which represents
10% of all acute myeloid leukemias. This test
may be used as a diagnostic tool, minimum
residual disease testing, or to predict
remission or detect relapse. It may be used to
monitor therapeutic response to all-trans
retinoic acid (ATRA). |
Acute promyelocytic leukemia (APL) is a
distinctive form of acute myelogenous leukemia
(AML). It accounts for approximately ten percent
of AML and is characterized by a proliferation
of malignant promyelocytes in the bone marrow,
often with a discrepant leukopenic peripheral
blood smear. APL is classified as AML or as M3
in the FAB scheme for acute leukemias. Patients
with APL have distinctive clinical features.
These individuals are generally younger than the
typical AML patient, have a better prognosis,
and almost always have disseminated
intravascular coagulation (DIC). This
coagulopathy becomes more severe with
chemotherapy and may lead to patient demise
during treatment. Therefore, proper
subclassification of acute leukemia as APL is
critical for optimal patient management (i.e.,
to alert the clinician that there is a
significant risk of DIC). In addition,
alternative strategies are used by
hematologists/oncologists to treat APL.
Specifically, all-trans retinoic acid (ATRA), a
relatively non-toxic agent, permits myeloid
differentiation of the leukemic promyelocytes
and is used as a first-line agent in the
treatment of this entity; this is followed by
standard chemotherapy. In summary, immediate
patient survival and important clinical
decisions are based on accurate diagnosis of
APL. Cytogenetic and molecular tests can be used
to establish a definitive diagnosis of APL.
There is a strong association of t(15;17), and
its molecular equivalent PML/RARa gene
rearrangement, with this subtype of AML. In
fact, the utility of ATRA therapy is based on
changes induced in the retinoic acid receptor a
(RARa) gene by this translocation. Moreover, the
response to ATRA in patients with AAPL is
directly related to the presence of PML/RARa
gene rearrangement (i.e., some AML -- M3
classified in the FAB scheme -- do not have this
molecular characteristic and have no response to
ATRA). Therefore, the molecular definition of
APL appears to have more clinical relevance than
the morphologic one. |
|
|
TEST SCHEDULES
