Medical Genetics
16 遗传与肿瘤发生
Cancer Genetics
Medical Genetics
The ancient Greeks believed that
cancer was caused by too much body
fluid they called "black bile."
Medical Genetics
Doctors in the seventeenth and
eighteenth centuries suggested that
parasites caused cancer,Today,
doctors understand more about the
link between cancer and genetics,
Medical Genetics
Viruses,ultraviolet (UV) radiation,and
chemicals can all damage genes in the
human body,If particular genes are
affected,a person can develop cancer,
Understanding how genes cause cancer,
though,first requires a basic
understanding of several genetic terms
and concepts,
Medical Genetics
1,General
Cancer is a very common
disease,affecting about 1 in 3
individuals,and about half the
people that contract cancer will die
as a direct result of their disease,
Medical Genetics
For the most part,cancer arises
from a single cell,that is,cancer is a
clonal disease,The average human
being contains about 1014 cells (i.e.,
100,000,000,000,000 cells),any one
of which could,in principle,become
a cancer cell,if it acquired the right
sort of mutations while it still had the
potential to proliferate,
Medical Genetics
Therefore,the cancer cell arises
and progresses once out of a
possible 1014 cellular targets,That
only happens in 1 in 3 people,Even
then it usually takes 60 or 70 years
to occur,
Medical Genetics
Medical Genetics
Tumors are hereditary
Hereditary retinoblastoma is an
autosomal dominant trait in which
susceptibility to retinoblastoma is
inherited,This is an unusual "dominant"
trait in that a mutation in one RB gene is
not sufficient to cause symptoms,but
mutations in the second allele often arise
during development,
Medical Genetics
Medical Genetics
Offspring have a 50% chance of
receiving the mutant gene from a
heterozygous parent,and 90% of carriers
will develop retinoblastoma,usually in
both eyes,The hereditary form is also
associated with a high risk for other
cancers especially of the bone and fibrous
tissues (osteosarcomas and fibrosarcoma,
Medical Genetics
Sporadic retinoblastoma is a
trait in which the affected individual
has not inherited any mutant alleles
of the retinoblastoma gene,
Medical Genetics
The mutations occur after birth
and result in tumor formation,
Tumors usually develop in only one
eye and patients are not at high risk
for other cancers,Both alleles need
to be mutated in a single cell,and
that is why this form typically occurs
only in one eye,
Medical Genetics
Medical Genetics
Chromosome and tumors
Detailed studies of the Philadelphia
chromosome show that most of chromosome 22
has been translocated onto the long arm of
chromosome 9,In addition,the small distal
portion of the short arm of chromosome 9 is
translocated to chromosome 22,This
translocation,which is found only in tumor cells,
indicates that a patient has chronic myelogenous
leukemia (CML),In CML,the cells that produce
blood cells for the body (the hematopoietic cells)
grow uncontrollably,leading to cancer,
Medical Genetics
Medical Genetics
Medical Genetics
The connection between this
chromosomal abnormality and CML
was clarified by studying the genes
located on the chromosomes at the
sites of the translocation breakpoints,
Medical Genetics
In one of the translocated
chromosomes,part of a gene called
abl is moved from its normal location
on chromosome 9 to a new location
on chromosome 22,This breakage
and reattachment leads to an altered
abl gene,The protein produced from
the mutant abl gene functions
improperly,leading to CML,
Medical Genetics
2,oncogene
Oncogenes are mutated forms of
genes that cause normal cells to
grow out of control and become
cancer cells,They are mutations of
certain normal genes of the cell
called proto-oncogenes,
Medical Genetics
Proto-oncogenes are the genes that
normally control how often a cell divides
and the degree to which it differentiates
(or specializes),When a proto-oncogene
mutates (changes) into an oncogene,it
becomes permanently "turned on" or
activated when it is not supposed to be,
When this occurs,the cell divides too
quickly,which can lead to cancer,
Medical Genetics
It may be helpful to think of a cell as
a car,For it to work properly,there need
to be ways to control how fast it goes,A
proto-oncogene normally functions in a
way that is similar to a gas pedal -- it
helps the cell grow and divide,An
oncogene could be compared to a gas
pedal that is stuck down,which causes the
cell to divide out of control,
Medical Genetics
The pathway for normal cell growth
starts with growth factor,which locks onto
a growth factor receptor,The signal from
the receptor is sent through a signal
transducer,A transcription factor is
produced,which causes the cell to begin
dividing,If any abnormality is detected,
the cell is made to commit suicide by a
programmed cell death regulator,
Medical Genetics
More than 100 oncogenes are
now recognized,and undoubtedly
more will be discovered in the future,
Scientists have divided oncogenes
into the 5 different classes,
Medical Genetics
Growth factors
These oncogenes produce factors
that stimulate cells to grow,The best
known of these is called sis,It leads
to the overproduction of a protein
called platelet-derived growth factor,
which stimulates cells to grow,
Medical Genetics
Growth factor receptors
These are normally turned "on"
or "off" by growth factors,When they
are "on," they stimulate the cell to
grow,Certain mutations in the genes
that produce these cause them to
always be "on." In other cases,the
genes are amplified,
Medical Genetics
This means that instead of the
usual 2 copies of the gene,there
may be several extras,resulting in
too many growth factor receptor
molecules,As a result,the cells
become overly sensitive to growth-
promoting signals,
Medical Genetics
The best known examples of growth
factor receptor gene amplification are erb
B and erb B-2,These are sometimes
known as epidermal growth factor
receptor and HER2/neu,HER2/neu gene
amplification is an important abnormality
seen in about one third of breast cancers,
Both of these oncogenes are targets of
newly developed anti-cancer treatments,
Medical Genetics
Signal transducers
These are the intermediate
pathways between the growth factor
receptor and the cell nucleus where
the signal is received,Like growth
factor receptors,these can be turned
on or off,When they are abnormal in
cancer cells,they are turned on,
Medical Genetics
Transcription factors
These are the final molecules in
the chain that tell the cell to divide,
These molecules act on the DNA and
control which genes are active in
producing RNA and protein,
Medical Genetics
The best known of these is called
myc,In lung cancer,leukemia,
lymphoma,and a number of other
cancer types,myc is often overly
activated and stimulates cell division,
Medical Genetics
Two well known signal
transducers are abl and ras,Abl is
activated in chronic myelocytic
leukemia and is the target of the
most successful drug for this disease,
imatinib or Gleevec,Abnormalities of
ras are found in many cancers,
Medical Genetics
Programmed cell death regulators
These molecules prevent a cell
from committing suicide when it
becomes abnormal,When these
genes are overactive they prevent
the cell from going through the
suicide process,
Medical Genetics
This leads to an overgrowth of
abnormal cells,which can then
become cancerous,The most well
described one is called bcl-2,It is
often activated in lymphoma cells,
Medical Genetics
3,Tumor Suppressor Genes
Tumor suppressor genes are
normal genes that slow down cell
division,repair DNA mistakes,and
tell cells when to die (a process
known as apoptosis or programmed
cell death),
Medical Genetics
When tumor suppressor genes do
work properly,cells can grow out of
control,which can lead to cancer,
About 30 tumor suppressor genes
have been identified,including p53,
BRCA1,BRCA2,APC,and RB1,Some
of these will be described in more
detail later on,
Medical Genetics
A tumor suppressor gene is like
the brake pedal on a car – it
normally keeps the cell from dividing
too quickly just as a brake keeps a
car from going too fast,When
something goes wrong with the gene,
such as a mutation,cell division can
get out of control,
Medical Genetics
An important difference
between oncogenes and tumor
suppressor genes is that oncogenes
result from the activation (turning on)
of proto-oncogenes,but tumor
suppressor genes cause cancer when
they are inactivated (turned off),
Medical Genetics
Another major difference is that
while the overwhelming majority of
oncogenes develop from mutations in
normal genes (proto-oncogenes)
during the life of the individual
(acquired mutations),abnormalities
of tumor suppressor genes can be
inherited as well as acquired,
Medical Genetics
Types of Tumor Suppressor Genes
Genes that control cell division
Genes that repair DNA
Cell "suicide" genes
Medical Genetics
Genes that control cell division
Some tumor suppressor genes
help control cell growth and
reproduction,The RB1
(retinoblastoma) gene is an example
of such a gene,Abnormalities of the
RB1 gene can lead to a type of eye
cancer (retinoblastoma) in infants,as
well as to other cancers,
Medical Genetics
Genes that repair DNA
A second group of tumor
suppressor genes is responsible for
repairing DNA damage,Every time a
cell prepares to divide into 2 new
cells,it must duplicate its DNA,
Medical Genetics
This process is not perfect,and
copying errors sometimes occur,
Fortunately,cells have DNA repair
genes,which make proteins that
proofread DNA,But if the genes
responsible for the repair are faulty,
then the DNA can develop
abnormalities that may lead to
cancer,
Medical Genetics
When DNA repair genes do work,
mutations can slip by,allowing oncogenes
and abnormal tumor suppressor genes to
be produced,The genes responsible for
HNPCC (hereditary nonpolyposis colon
cancer) are examples of DNA repair gene
defects,When these genes do not repair
the errors in DNA,HNPCC can result,
HNPCC accounts for up to 5% of all colon
cancers and some endometrial cancers,
Medical Genetics
Cell "suicide" genes
If there is too much damage to
a cell DNA to be fixed by the DNA
repair genes,the p53 tumor
suppressor gene is responsible for
destroying the cell by a process
sometimes described as "cell
suicide."
Medical Genetics
Other names for this process are
programmed cell death or apoptosis,
If the p53 gene is not working
properly,cells with DNA damage that
has not been repaired continue to
grow and can eventually become
cancerous,
Medical Genetics
Abnormalities of the p53 gene
are sometimes inherited,such as in
the Li-Fraumeni syndrome (LFS),
People with LFS have a higher risk
for developing a number of cancers,
including soft-tissue and bone
sarcomas,brain tumors,breast
cancer,adrenal gland cancer,and
leukemia,
Medical Genetics
Many sporadic (not inherited)
cancers such as lung cancers,colon
cancers,breast cancers as well as
others often have mutated p53
genes within the tumor,
Medical Genetics
Inherited Abnormalities of Tumor
Suppressor Genes
Inherited abnormalities of
tumor suppressor genes have been
found in several cancers that tend to
run in families,
Medical Genetics
In addition to mutations in p53,
RB1,and the genes involved in
HNPCC,several other mutations in
tumor suppressor genes can be
inherited,
Medical Genetics
A defective APC gene causes
familial polyposis,a condition in
which people develop hundreds or
thousands of colon polyps,some of
which may eventually acquire several
sporadic mutations and turn into
colon cancer,
Medical Genetics
Abnormalities of the BRCA genes
account for 5% to 10% of breast
cancers,There are also many other
examples of inherited tumor
suppressor gene mutations,and
more are being discovered each year,
Medical Genetics
Non-inherited mutations of tumor
suppressor genes
Mutations of tumor suppressor
genes have been found in many
cancers.,
Medical Genetics
For example,abnormalities of
the p53 gene have been found in
over 50% of human cancers,
Acquired mutations (those which
happen during a person life) of the
p53 gene appear to be involved in a
wide range of cancers,including lung,
colorectal,and breast cancer,as well
as many others,
Medical Genetics
The p53 gene is believed to be
among the most frequently mutated
genes in human cancer,However,
acquired changes in many other
tumor suppressor genes also
contribute to the development of
sporadic (not inherited) cancers,
Medical Genetics
Inherited cancer Abnormal gene Other non-inherited cancers seen with this gene
Retinoblastoma RBI Many different cancers
Li-Fraumeni Syndrome (sarcomas,
brain tumors,leukemia) P53 Many different cancers
Melanoma INK4a Many different cancers
Colorectal cancer (due to familial
polyposis) APC Most colorectal cancers
Colorectal cancer (without
polyposis)
MLH1,MSH2,or
MSH6
Colorectal,gastric,endometrial
cancers
Breast and/or ovarian BRCA1,BRCA2 Only rare ovarian cancers
Wilms Tumor WTI Wilms tumors
Nerve tumors,including brain NF1,NF2 Small numbers of colon cancers,melanomas,neuroblastoma
Kidney cancer VHL Certain types of kidney cancers
Medical Genetics
Oncogene/Tumor
Suppressor Gene Related Cancers
BRCA1,BRCA2 Breast and ovarian cancer
bcr-abl Chronic myelogenous leukemia
bcl-2 B-cell lymphoma
HER2/neu (erbB-2) Breast cancer,ovarian cancer,others
N-myc Neuroblastoma
EWS Ewing tumor
C-myc Burkitt lymphoma,others
p53 Brain tumors,skin cancers,lung cancer,head and neck cancers,others
MLH1,MSH2 Colorectal cancers
APC Colorectal cancers
Medical Genetics
4,Multi-stage Carcinogenesis
Multi-stage carcinogenesis starts with the
development of initiated cells after interactions of
acarcinogenic agent with normal (target) cells,
The initiated cells have the ability to clonally
expand and act as precursors for additional
alterations,In different model systems initiated
cells have shown some of the following
characteristics,
1,Increased proliferative capabilities
2,Resistance to apoptotic stimuli
3,Resistance to other inducers of cell toxicity
4,Increased life-span
Medical Genetics
Medical Genetics
Medical Genetics
Medical Genetics
Medical Genetics
16 遗传与肿瘤发生
Cancer Genetics
Medical Genetics
The ancient Greeks believed that
cancer was caused by too much body
fluid they called "black bile."
Medical Genetics
Doctors in the seventeenth and
eighteenth centuries suggested that
parasites caused cancer,Today,
doctors understand more about the
link between cancer and genetics,
Medical Genetics
Viruses,ultraviolet (UV) radiation,and
chemicals can all damage genes in the
human body,If particular genes are
affected,a person can develop cancer,
Understanding how genes cause cancer,
though,first requires a basic
understanding of several genetic terms
and concepts,
Medical Genetics
1,General
Cancer is a very common
disease,affecting about 1 in 3
individuals,and about half the
people that contract cancer will die
as a direct result of their disease,
Medical Genetics
For the most part,cancer arises
from a single cell,that is,cancer is a
clonal disease,The average human
being contains about 1014 cells (i.e.,
100,000,000,000,000 cells),any one
of which could,in principle,become
a cancer cell,if it acquired the right
sort of mutations while it still had the
potential to proliferate,
Medical Genetics
Therefore,the cancer cell arises
and progresses once out of a
possible 1014 cellular targets,That
only happens in 1 in 3 people,Even
then it usually takes 60 or 70 years
to occur,
Medical Genetics
Medical Genetics
Tumors are hereditary
Hereditary retinoblastoma is an
autosomal dominant trait in which
susceptibility to retinoblastoma is
inherited,This is an unusual "dominant"
trait in that a mutation in one RB gene is
not sufficient to cause symptoms,but
mutations in the second allele often arise
during development,
Medical Genetics
Medical Genetics
Offspring have a 50% chance of
receiving the mutant gene from a
heterozygous parent,and 90% of carriers
will develop retinoblastoma,usually in
both eyes,The hereditary form is also
associated with a high risk for other
cancers especially of the bone and fibrous
tissues (osteosarcomas and fibrosarcoma,
Medical Genetics
Sporadic retinoblastoma is a
trait in which the affected individual
has not inherited any mutant alleles
of the retinoblastoma gene,
Medical Genetics
The mutations occur after birth
and result in tumor formation,
Tumors usually develop in only one
eye and patients are not at high risk
for other cancers,Both alleles need
to be mutated in a single cell,and
that is why this form typically occurs
only in one eye,
Medical Genetics
Medical Genetics
Chromosome and tumors
Detailed studies of the Philadelphia
chromosome show that most of chromosome 22
has been translocated onto the long arm of
chromosome 9,In addition,the small distal
portion of the short arm of chromosome 9 is
translocated to chromosome 22,This
translocation,which is found only in tumor cells,
indicates that a patient has chronic myelogenous
leukemia (CML),In CML,the cells that produce
blood cells for the body (the hematopoietic cells)
grow uncontrollably,leading to cancer,
Medical Genetics
Medical Genetics
Medical Genetics
The connection between this
chromosomal abnormality and CML
was clarified by studying the genes
located on the chromosomes at the
sites of the translocation breakpoints,
Medical Genetics
In one of the translocated
chromosomes,part of a gene called
abl is moved from its normal location
on chromosome 9 to a new location
on chromosome 22,This breakage
and reattachment leads to an altered
abl gene,The protein produced from
the mutant abl gene functions
improperly,leading to CML,
Medical Genetics
2,oncogene
Oncogenes are mutated forms of
genes that cause normal cells to
grow out of control and become
cancer cells,They are mutations of
certain normal genes of the cell
called proto-oncogenes,
Medical Genetics
Proto-oncogenes are the genes that
normally control how often a cell divides
and the degree to which it differentiates
(or specializes),When a proto-oncogene
mutates (changes) into an oncogene,it
becomes permanently "turned on" or
activated when it is not supposed to be,
When this occurs,the cell divides too
quickly,which can lead to cancer,
Medical Genetics
It may be helpful to think of a cell as
a car,For it to work properly,there need
to be ways to control how fast it goes,A
proto-oncogene normally functions in a
way that is similar to a gas pedal -- it
helps the cell grow and divide,An
oncogene could be compared to a gas
pedal that is stuck down,which causes the
cell to divide out of control,
Medical Genetics
The pathway for normal cell growth
starts with growth factor,which locks onto
a growth factor receptor,The signal from
the receptor is sent through a signal
transducer,A transcription factor is
produced,which causes the cell to begin
dividing,If any abnormality is detected,
the cell is made to commit suicide by a
programmed cell death regulator,
Medical Genetics
More than 100 oncogenes are
now recognized,and undoubtedly
more will be discovered in the future,
Scientists have divided oncogenes
into the 5 different classes,
Medical Genetics
Growth factors
These oncogenes produce factors
that stimulate cells to grow,The best
known of these is called sis,It leads
to the overproduction of a protein
called platelet-derived growth factor,
which stimulates cells to grow,
Medical Genetics
Growth factor receptors
These are normally turned "on"
or "off" by growth factors,When they
are "on," they stimulate the cell to
grow,Certain mutations in the genes
that produce these cause them to
always be "on." In other cases,the
genes are amplified,
Medical Genetics
This means that instead of the
usual 2 copies of the gene,there
may be several extras,resulting in
too many growth factor receptor
molecules,As a result,the cells
become overly sensitive to growth-
promoting signals,
Medical Genetics
The best known examples of growth
factor receptor gene amplification are erb
B and erb B-2,These are sometimes
known as epidermal growth factor
receptor and HER2/neu,HER2/neu gene
amplification is an important abnormality
seen in about one third of breast cancers,
Both of these oncogenes are targets of
newly developed anti-cancer treatments,
Medical Genetics
Signal transducers
These are the intermediate
pathways between the growth factor
receptor and the cell nucleus where
the signal is received,Like growth
factor receptors,these can be turned
on or off,When they are abnormal in
cancer cells,they are turned on,
Medical Genetics
Transcription factors
These are the final molecules in
the chain that tell the cell to divide,
These molecules act on the DNA and
control which genes are active in
producing RNA and protein,
Medical Genetics
The best known of these is called
myc,In lung cancer,leukemia,
lymphoma,and a number of other
cancer types,myc is often overly
activated and stimulates cell division,
Medical Genetics
Two well known signal
transducers are abl and ras,Abl is
activated in chronic myelocytic
leukemia and is the target of the
most successful drug for this disease,
imatinib or Gleevec,Abnormalities of
ras are found in many cancers,
Medical Genetics
Programmed cell death regulators
These molecules prevent a cell
from committing suicide when it
becomes abnormal,When these
genes are overactive they prevent
the cell from going through the
suicide process,
Medical Genetics
This leads to an overgrowth of
abnormal cells,which can then
become cancerous,The most well
described one is called bcl-2,It is
often activated in lymphoma cells,
Medical Genetics
3,Tumor Suppressor Genes
Tumor suppressor genes are
normal genes that slow down cell
division,repair DNA mistakes,and
tell cells when to die (a process
known as apoptosis or programmed
cell death),
Medical Genetics
When tumor suppressor genes do
work properly,cells can grow out of
control,which can lead to cancer,
About 30 tumor suppressor genes
have been identified,including p53,
BRCA1,BRCA2,APC,and RB1,Some
of these will be described in more
detail later on,
Medical Genetics
A tumor suppressor gene is like
the brake pedal on a car – it
normally keeps the cell from dividing
too quickly just as a brake keeps a
car from going too fast,When
something goes wrong with the gene,
such as a mutation,cell division can
get out of control,
Medical Genetics
An important difference
between oncogenes and tumor
suppressor genes is that oncogenes
result from the activation (turning on)
of proto-oncogenes,but tumor
suppressor genes cause cancer when
they are inactivated (turned off),
Medical Genetics
Another major difference is that
while the overwhelming majority of
oncogenes develop from mutations in
normal genes (proto-oncogenes)
during the life of the individual
(acquired mutations),abnormalities
of tumor suppressor genes can be
inherited as well as acquired,
Medical Genetics
Types of Tumor Suppressor Genes
Genes that control cell division
Genes that repair DNA
Cell "suicide" genes
Medical Genetics
Genes that control cell division
Some tumor suppressor genes
help control cell growth and
reproduction,The RB1
(retinoblastoma) gene is an example
of such a gene,Abnormalities of the
RB1 gene can lead to a type of eye
cancer (retinoblastoma) in infants,as
well as to other cancers,
Medical Genetics
Genes that repair DNA
A second group of tumor
suppressor genes is responsible for
repairing DNA damage,Every time a
cell prepares to divide into 2 new
cells,it must duplicate its DNA,
Medical Genetics
This process is not perfect,and
copying errors sometimes occur,
Fortunately,cells have DNA repair
genes,which make proteins that
proofread DNA,But if the genes
responsible for the repair are faulty,
then the DNA can develop
abnormalities that may lead to
cancer,
Medical Genetics
When DNA repair genes do work,
mutations can slip by,allowing oncogenes
and abnormal tumor suppressor genes to
be produced,The genes responsible for
HNPCC (hereditary nonpolyposis colon
cancer) are examples of DNA repair gene
defects,When these genes do not repair
the errors in DNA,HNPCC can result,
HNPCC accounts for up to 5% of all colon
cancers and some endometrial cancers,
Medical Genetics
Cell "suicide" genes
If there is too much damage to
a cell DNA to be fixed by the DNA
repair genes,the p53 tumor
suppressor gene is responsible for
destroying the cell by a process
sometimes described as "cell
suicide."
Medical Genetics
Other names for this process are
programmed cell death or apoptosis,
If the p53 gene is not working
properly,cells with DNA damage that
has not been repaired continue to
grow and can eventually become
cancerous,
Medical Genetics
Abnormalities of the p53 gene
are sometimes inherited,such as in
the Li-Fraumeni syndrome (LFS),
People with LFS have a higher risk
for developing a number of cancers,
including soft-tissue and bone
sarcomas,brain tumors,breast
cancer,adrenal gland cancer,and
leukemia,
Medical Genetics
Many sporadic (not inherited)
cancers such as lung cancers,colon
cancers,breast cancers as well as
others often have mutated p53
genes within the tumor,
Medical Genetics
Inherited Abnormalities of Tumor
Suppressor Genes
Inherited abnormalities of
tumor suppressor genes have been
found in several cancers that tend to
run in families,
Medical Genetics
In addition to mutations in p53,
RB1,and the genes involved in
HNPCC,several other mutations in
tumor suppressor genes can be
inherited,
Medical Genetics
A defective APC gene causes
familial polyposis,a condition in
which people develop hundreds or
thousands of colon polyps,some of
which may eventually acquire several
sporadic mutations and turn into
colon cancer,
Medical Genetics
Abnormalities of the BRCA genes
account for 5% to 10% of breast
cancers,There are also many other
examples of inherited tumor
suppressor gene mutations,and
more are being discovered each year,
Medical Genetics
Non-inherited mutations of tumor
suppressor genes
Mutations of tumor suppressor
genes have been found in many
cancers.,
Medical Genetics
For example,abnormalities of
the p53 gene have been found in
over 50% of human cancers,
Acquired mutations (those which
happen during a person life) of the
p53 gene appear to be involved in a
wide range of cancers,including lung,
colorectal,and breast cancer,as well
as many others,
Medical Genetics
The p53 gene is believed to be
among the most frequently mutated
genes in human cancer,However,
acquired changes in many other
tumor suppressor genes also
contribute to the development of
sporadic (not inherited) cancers,
Medical Genetics
Inherited cancer Abnormal gene Other non-inherited cancers seen with this gene
Retinoblastoma RBI Many different cancers
Li-Fraumeni Syndrome (sarcomas,
brain tumors,leukemia) P53 Many different cancers
Melanoma INK4a Many different cancers
Colorectal cancer (due to familial
polyposis) APC Most colorectal cancers
Colorectal cancer (without
polyposis)
MLH1,MSH2,or
MSH6
Colorectal,gastric,endometrial
cancers
Breast and/or ovarian BRCA1,BRCA2 Only rare ovarian cancers
Wilms Tumor WTI Wilms tumors
Nerve tumors,including brain NF1,NF2 Small numbers of colon cancers,melanomas,neuroblastoma
Kidney cancer VHL Certain types of kidney cancers
Medical Genetics
Oncogene/Tumor
Suppressor Gene Related Cancers
BRCA1,BRCA2 Breast and ovarian cancer
bcr-abl Chronic myelogenous leukemia
bcl-2 B-cell lymphoma
HER2/neu (erbB-2) Breast cancer,ovarian cancer,others
N-myc Neuroblastoma
EWS Ewing tumor
C-myc Burkitt lymphoma,others
p53 Brain tumors,skin cancers,lung cancer,head and neck cancers,others
MLH1,MSH2 Colorectal cancers
APC Colorectal cancers
Medical Genetics
4,Multi-stage Carcinogenesis
Multi-stage carcinogenesis starts with the
development of initiated cells after interactions of
acarcinogenic agent with normal (target) cells,
The initiated cells have the ability to clonally
expand and act as precursors for additional
alterations,In different model systems initiated
cells have shown some of the following
characteristics,
1,Increased proliferative capabilities
2,Resistance to apoptotic stimuli
3,Resistance to other inducers of cell toxicity
4,Increased life-span
Medical Genetics
Medical Genetics
Medical Genetics
Medical Genetics
Medical Genetics
