Acute Myelogenous Leukemia (AML) (Translocation 8/21 probe
- F.I.S.H)
Acute myelogenous leukemia (AML) is a fast-growing cancer
of the blood and bone marrow. In AML, the bone marrow makes
many unformed cells called blasts. Blasts normally develop
into white blood cells that fight infection. However, the
blasts are abnormal in AML. They do not develop and cannot
fight infections. The bone marrow may also make abnormal red
blood cells and platelets. The number of abnormal cells (or
leukemia cells) grows quickly. They crowd out the normal red
blood cells, white blood cells and platelets the body needs.
AML is the most common acute leukemia affecting adults, and
its incidence increases with age. Although AML is a relatively
rare disease, accounting for approximately 1.2% of cancer
deaths in the United States, its incidence is expected to
increase as the population ages.
Translocation of (8;21)(q22;q22) is the most frequently observed
karyotypic abnormality associated with acute myeloid leukemia
(AML). Clinically, this type of AML often shows eosinophilia
and has a high complete remission rate with conventional chemotherapy.
t(8;21) AML is also frequently associated with additional
karyotypic aberrations, such as a loss of the sex chromosome;
however, it is unclear whether these aberrations change the
biological and clinical characteristics of t(8;21) AML.
BRCA1 and BRCA2
Approximately 10 to 15 percent of all breast cancers are thought
to be familial and about one third of these cases are due
to an inherited mutation in a BRCA1 or BRCA2 breast cancer
susceptibility gene. BRCA1 and 2 mutations are associated
with early-onset breast cancer, and some experts call for
aggressive Screening of affected persons.
BRCA1 is a gene on chromosome 17 that is known to be involved
in tumor suppression. A woman with certain known mutations
in BRCA1 has a lifetime risk of 56 to 85 percent for breast
cancer and an increased risk of ovarian cancer. Of women with
breast cancer, a BRCA1 mutation has been found in 0.3 percent
(one of 333) and of women in the general population, in 0.12
percent (one of 833). In Ashkenazi Jewish women (most Jewish
people in the United States are of this Eastern European origin),
BRCA1 mutations occur in 1 percent.
BRCA2 is another susceptibility gene for breast cancer and
is found on chromosome 13. Mutations in BRCA2 confer an elevated
breast cancer risk similar to that occurring with BRCA1 mutations.
As with BRCA1, BRCA2 is also found in 1 percent of Ashkenazi
Jewish women. A woman’s lifetime chance of developing
breast and/or ovarian cancer is greatly increased if she inherits
an altered BRCA1 or BRCA2 gene.
Women with an inherited alteration in one of these genes may
also have an increased chance of developing colon cancer.
Men with an altered BRCA1 or BRCA2 gene also have an increased
risk of breast cancer (primarily if the alteration is in BRCA2),
and possibly prostate cancer. Alterations in the BRCA2 gene
have also been associated with an increased risk of lymphoma,
melanoma, and cancers of the pancreas, gallbladder, bile duct,
and stomach in some men and women.
In a family with a history of breast and/or ovarian cancer,
it may be most informative to first test a family member who
has the disease. If that person is found to have an altered
BRCA1 or BRCA2 gene, the specific change is referred to as
a "known mutation." Other family members can then
be tested to see if they also carry that specific alteration.
In this scenario, a positive test result indicates that a
person has inherited a known mutation in BRCA1 or BRCA2 and
has an increased risk of developing certain cancers, as described
above. However, a positive result provides information only
about a person's risk of developing cancer. It cannot tell
whether cancer will actually develop-or when. It is also impossible
to predict the effectiveness of special screening or preventive
medical procedures for people with alterations in BRCA1 or
BRCA2. Not all women who inherit an altered gene will develop
breast or ovarian cancer.
POSITIVE RESULT
A positive test result may have important health and social
implications for family members, including future generations.
Unlike most other medical tests, genetic tests can reveal
information not only about the person being tested, but also
about that person's relatives. Both men and women who inherit
an altered BRCA1 or BRCA2 gene, whether or not they get cancer
themselves, may pass the alteration on to their sons and daughters.
However, not all children of people who have an altered gene
will inherit the alteration.
NEGATIVE RESULT
A negative test result will be interpreted differently, depending
upon whether there is a known mutation in the family. If someone
in a family has a known mutation in BRCA1 or BRCA2, testing
other family members for that specific gene alteration can
provide information about their cancer risk. In this case,
if a family member tests negative for the known mutation in
that family, it is highly unlikely that they have an inherited
susceptibility to cancer. This test result is called a "true
negative." Having a true negative test result does not
mean that a person will not get cancer; it means that the
person's risk of cancer is the same as that of the general
population.
In cases where no known mutation in BRCA1 or BRCA2 has previously
been identified in a family with a history of breast and/or
ovarian cancer, a negative test is not informative. It is
not possible to tell whether a person has an alteration in
BRCA1 or BRCA2 that was not identified by the test (a false
negative), or whether the result is a true negative. In addition,
it is possible for people to have an alteration in a gene
other than BRCA1 or BRCA2 that increases their cancer risk,
but is not detectable by this test.
Burkitts Lymphoma (Translocation 8/14 probe - F.I.S.H)
Burkitt's lymphoma is cancer of the lymphatic system, which
can be further divided into Hodgkin's lymphoma and non-Hodgkin's
lymphoma (NHL)). Burkitt's lymphoma is classified under non-Hodgkin's
lymphoma.
Lymphatic system is an important part of our body that helps
fight infection. It is composed of the lymph nodes, the thymus
(a gland behind the breastbone), bone marrow and spleen, which
are connected by tiny lymph vessels. Lymph is a colourless
fluid that circulates in the lymphatic system. It contains
lymphocytes which are white blood cells that fight infection.
There are 2 types of lymphycytes: T cells and B cells. Burkitt's
lymphoma is a fast-growing non-Hodgkin's lymphoma that originates
from B cells.
Burkitt's lymphoma is a relatively rare disease in Western
countries, but is common in Central Africa. It makes up 0.3-1.3%
of all non-Hodgkin's Lymphoma. The predicted number of new
cases of Burkitt's lymphoma in Australia is 12 per year.
Although a rare condition in adults, Burkitt's lymphoma is
relatively common in children, making up about 30% of all
childhood non-Hodgkin lymphoma. It more commonly affects the
male, with the male to female ratio being around 2-3 to 1.
It is also seen more in AIDS patients.
Recent molecular analyses of Burkitt lymphomas carrying the
t(8;14) chromosome translocation have indicated that a dichotomy
exists regarding the molecular mechanisms by which the translocations
occur. Most sporadic Burkitt tumors carry translocations that
apparently arise due to mistakes in the immunoglobulin isotype-switching
process.
Chronic myelogenous leukemia (CML) (Bcr/Abl dual probe)
Chronic myelogenous leukemia (CML) also known as chronic myeloid
leukemia or chronic granulocytic leukemia) is a cancer of
the blood system in which too many white blood cells (WBCs)
are made in the bone marrow. In the early stages of CML (the
chronic phase), these excess WBCs mature normally. In contrast,
excess WBCs in late CML (the accelerated and acute phases)
do not mature.
The American Cancer Society estimates that in 2007 there will
be about 4,570 new cases of chronic myelogenous leukemia in
the United States, and that about 490 will die of the disease.
With the average age of people with CML around 66 years, CML
mostly affects adults, although 2 percent of CML patients
are children.
In almost everyone with CML, the genetic material (chromosomes)
in the leukemia cells has an abnormal feature called the Philadelphia
chromosome (right).
The Philadelphia chromosome results from a mutation called
a translocation (two chromosomes break, then parts from each
chromosome switch places). In CML, the translocation occurs
between chromosomes 9 and 22 (human DNA is packaged in 23
pairs of chromosomes) and produces a new, abnormal gene called
BCR-ABL. This abnormal gene produces Bcr-Abl tyrosine kinase,
an abnormal protein that causes the excess WBCs typical of
CML.
The Philadelphia chromosome is an acquired mutation —
that is, a person is not born with it and it is not passed
on to their children. Exactly why the Philadelphia chromosome
forms is unknown in most cases, although exposure to ionizing
radiations (such as during the atomic bomb explosions in Japan)
has been shown to cause CML.
Melanoma-Genetic Test for Hereditary Melanoma
Melanoma is a form of skin cancer that is highly curable when
caught early. While melanoma only accounts for a small portion
of skin cancer cases, it is the cause of most skin cancer-related
deaths. The number of new melanomas diagnosed in the United
States is rising rapidly, with over 59,000 new cases diagnosed
each year.
While the cause of all melanomas is not known, it is estimated
that 10 percent of melanomas are associated with familial
or inherited syndromes. Most hereditary melanoma is believed
to be caused by mutations in a specific gene called p16. The
p16 gene, when functioning normally, protects against unchecked
cell growth. However, when the p16 gene is damaged, cells
are allowed to grow in an unregulated way and cause cancer.
Alterations in this gene significantly increase your risk
of melanoma and pancreatic cancer.
Many individuals are unaware of their inherited risk, although
they may be aware of a cancer history in their family. Whether
or not you've had cancer, the following conditions might indicate
hereditary cancer risk:
-Two or more melanomas in an individual or family
-Melanoma and pancreatic cancer in an individual or family
-Relatives of a p16 mutation carrier
We're all born with two copies of about 30,000 different genes,
one copy of each gene from our mother and the other from our
father. When we have inherited a mutation in a specific gene
from either parent, it makes us more susceptible to certain
cancers. A person with these gene mutations has a higher risk
of developing cancer and also may pass that altered gene on
to his or her children.
Colon Cancer (MLH1/ MSH 2) MLH1/ MSH 2
Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal
dominant inherited colorectal cancer syndrome that accounts
for 5% to 8% of all colorectal cancers. Families with HNPCC
are at high risk for developing other cancers, such as endometrial,
ovarian, gastric, small bowel, renal pelvis, and ureter.
HNPCC is associated with germline mutations in mismatch repair
genes. MLH1/MSH2 mutations account for 90% of all mutations
found in HNPCC; however, the prevalence of MLH1 and MSH2 mutations
in these families is only about 15% to 60%. Other genes, notably
MSH6, PMS1, and PMS2 have also being described in a small
number of individuals. MSH6 mutations are commonly associated
with atypical HNPCC.
Late age of onset of HNPCC cancers, predominance of endometrial
cancer in female carriers, and microsatellite instability
(MSI) predominantly at mononucleotide repeats with low penetrance
are some of the characteristics of MSH6 mutation carriers.
MSH2 and MLH1 mutation positive individuals have approximately
a 70% to 90% lifetime risk of developing colorectal cancer.
MSH2 mutation carriers have a higher risk of developing
extracolonic HNPCC cancers, such as endometrial cancer in
women. Studies have validated the usefulness of these criteria
for HNPCC genetic testing.
Even though molecular genetics of HNPCC is still a developing
field, the information available has been used to develop
guidelines for genetic testing and surveillance for high-risk
individuals and families. Identification of families who
are at high-risk enables health care providers to recommend
appropriate screening practices and provide patients with
options of suitable chemoprevention and prophylactic surgeries.
Clinically, genetic testing is useful to distinguish between
high-risk individuals who need aggressive screening and
management and average-risk individuals whose screening
recommendations are the same as those for the general population.
People with the HNPCC gene mutations have an 80% lifetime
risk of developing colorectal cancer. In 1990, the International
Collaborative Group (ICG) met in Amsterdam and established
the criteria for defining HNPCC families: 1) one family
member diagnosed with colorectal cancer before age 50; 2)
two affected generations; 3) three affected relatives, one
of them a first-degree relative of the other two. Interpreting
these test results can be difficult, but can have the potential
to guide a person’s future medical and lifestyle decisions.
It is important for people to understand the meaning of
the results and also have a clear idea of how they will
use these results.
If a HNPCC mutation is identified in an affected family
member, then at-risk family members may choose to undergo
testing for the same mutation.
POSITIVE RESULT
While a positive test can indicate an increased risk of
developing colorectal cancer, a negative test may not be
as informative. Individuals with HNPCC tend to develop cancer
earlier in life than those who do not have HNPCC; therefore,
it is recommended that screening in these individuals begin
earlier in life. Because cancers in these individuals tend
to develop more rapidly, the screening procedures should
be performed at shorter intervals to ensure the greatest
chance of detecting the cancer early when it is most treatable.
NEGATIVE RESULT
A negative test result does not necessarily indicate freedom
from risk. If a family has a known mutation, a negative
result may mean that a person does not have an inherited
risk; however, it could also mean that current gene testing
is not yet sensitive enough to detect the mutation. In addition,
these individuals could still have a mutation in one of
the other HNPCC genes for which testing is not yet available.
Small Cell Cancer of Lung (EGFR mutation-F.I.S.H)
About 10% to 15% of all lung cancers are the small cell
lung cancer (SCLC), named for the small cells that make
up these cancers. Other names for SCLC are oat cell carcinoma
and small cell undifferentiated carcinoma.
SCLC often starts in the bronchi near the center of the
chest, and it tends to spread widely through the body fairly
early in the course of the disease. The cancer cells can
multiply quickly, form large tumors, and spread to lymph
nodes and other organs, such as the bones, brain, adrenal
glands, and liver. This is important because it means that
surgery is rarely an option (and never the only treatment
given). Treatment must include drugs to try to kill the
widespread disease.
Small cell lung cancer is almost always caused by smoking.
It is very rare for someone who has never smoked to have
small cell lung cancer.
Recently, the lung cancer treatment is based on mutations
in the epidermal growth factor receptor (EGFR) gene. It
is found that the non-small-cell lung cancers with EGFR
mutations display a two-to-three-fold increment in outcome
in comparison with non-small-cell lung cancers treated with
chemot herapy, in which median survival is 11 months, time-to-progression
is 5 months, and response 20-30%.
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