Biochemical Mechanisms in Cancer Exam Questions and Answers.
f - Answers-
Bloom syndrome - predisposition to the development of cancer. AR inheritance. Carrier
frequency in Eastern European Jewish (Ashkenazi Jewish) ancestry - 1/100. The
mutations in the BLM gene inactivate the BLM protein's DNA helicase activity or nullify
protein expression. Lack of BLM protein or protein activity leads to an increase
mutations. List common characteristics of Bloom syndrome! - AnswersCommon
characteristics of Bloom syndrome - (1) short stature (2) rash develops early in life in
sun-exposed areas of the skin. (3) high-pitched voice (4) distinct facial features: narrow
face, micrognathism, prominent nose, ears (5) hypo- hyper-pigmented skin areas, cafe-
au-lait spots; (6) telangiectasias, also in the eyes (7) moderate immune deficiency - in
certain Ig - recurrent pneumonia, ear infections (8) hypogonadism - failure to produce
sperm, premature menopause
Fanconi anemia (FA) - genetic disease. Incidence of 1/350,000 births, with a higher
frequency in Ashkenazi Jews and Afrikaners in South Africa. FA is the result of a
genetic defect in a cluster of proteins responsible for DNA repair. As a result, the
majority of FA patients develop cancer - acute myelogenous leukemia, and 90%
develop bone marrow failure by age 40. 60-75% of FA patients have congenital defects,
commonly short stature, abnormalities of the skin, arms, head, eyes, kidneys, and ears,
and developmental disabilities. 75% of FA patients have some form of endocrine
problem, with varying degrees of severity. Median age of death 30 years. -
AnswersBecause of the genetic defect in DNA repair, cells from people with FA are
sensitive to drugs that treat cancer by DNA crosslinking, such
as mitomycin C. ~ 1,000 persons worldwide currently suffer from the disease. The
carrier frequency in the Ashkenazi Jewish - 1/90. There are 15 genes responsible for FA
- like breast-cancer susceptibility gene BRCA2. They are involved in the recognition and
repair of damaged DNA; genetic defects leave them unable to repair DNA.
ONCOGENES - AnswersONCOGENES
What is Proto-oncogenes? - AnswersProto-oncogenes are normal cellular proteins that
work to regulate normal growth and development. If mutated or misexpressed, the
proto-oncogenes become oncogenes and lead to aberrant cell cycle control.
What functon of Fibroblast growth factor (FSF)? - AnswersFibroblast growth factor
(FSFs) are family of proteins that are normally expressed during the proliferation of cells
required for normal wound healing, but overexpression can lead to tumor formation.
What functon of Platelet-derived growth factor (PDGF)? - AnswersPlatelet-derived
growth factor (PDGF) is a polypeptide that is normally important for extracellular matrix
production, but overexpression may results in proliferation as result of autocrine
stimulation.
Epidermal growth factor receptors (EGFRs): there are at least members of this family of
tyrosine kinase receptors, erb b-1, erb b-2, erb b-3 - AnswersWhen mutated, lead to
aberrant signaling and growth in the absence of the cognate ligand (EGF).
Overexpression of the growth factor receptor erb b-1, also known as HER2/neu, is
associated with development of breast cansers. Patients who overexpress HER2 in
their breast tumors can be treated with monoclonal antibody to HER2 which block
, signaling through this oncogenic pathway. Name this drug. - AnswersTrastuzumab
(Herceptin)
One of the mechanism of oncogenesis is Gene amplification defined as overexpression
of proto-oncogenes. GA can result from aberrant duplication of their DNA sequences,
often resulting in several hundred copies of the proto-oncogene and abnormal growth.
These duplicated regions can be seen on the chromosome as homogeneous staining
regions (HSRs). - AnswersBreast cancers are routinely screened for the presence of an
amplified HER2/neu oncogene. HER2/neu expression has been associated with a poor
prognosis. However, patients with HER2/neu overexpression are candidates for
Herceptin therapy.
What encodes RET proto-oncogene? - AnswersRET is a receptor tyrosine kinase for
members of the glial cell line-derived neurotrophic factor family (GDNF) of extracellular
signalling molecules or ligands (GFLs)
Loss of function mutations in RET prot-oncogene are associated with? - AnswersRET
loss of function mutations are associated with the development of Hirschsprung's
disease
Gain of function mutations in RET prot-oncogene are associated with the autonomous
growth promoting signals in the absence of ligand binding and development of various
types of human cancer, including? - AnswersParathyroid hyperplasia. Multiple
endocrine neoplasia (MEN) syndrome, including MEN I, which is charcterized by
Pancreatic, Pituitary, and Parathyroid tumors (PPP), and MEN II (A,B), which is
characterized by Adrenal (pheochromocytoma), Thyroid, and Parathyroid tumors (ATP),
also MEN IIC - familial medullary thyroid carcinoma (FMTC).
What encodes Ras (Rat sarcoma) proto-oncogene? - AnswersA GTP-binding protein
anchored to the inner cell membrane via a covalently attached farnesyl moiety.
In the inactive state, Ras binds GDP. In stimulation of the cell by growth factor-ligand
interactions, Ras exchanges GDP for GTP, leading to activation of downstream
signaling events. - AnswersThe Ras protein has intrinsic GTPase activity, terminating
the signal transduction events when GTP is hydrolyzed back to GDP, returning Ras to
its inactive state. Alterations in the Ras gene can change the Ras protein so that it is no
longer able to break up and release the GTP. These changes can cause the the
pathway to be stuck in the "on" position
The ras gene is the most commonly mutated oncogene in cancer, with 10-20% of
tumors harboring mutations in ras. - AnswersMutant ras has been identified in cancers
of many different origins, including: pancreas (90%), colon (50%), thyroid (50%), lung
(30%), bladder (6%), ovarian (15%), breast, skin, liver, kidney, and some leukemias. It
is also possible that in the future, ras may be used to detect certain cancers.
Historically, pancreatic cancer has been difficult to diagnose. The identification of ras
mutations in the DNA of pancreatic cells shed into feces may enable clinicians to
differentiate between chronic pancreatitis and pancreatic cancer.
Nonreceptor tyrosine kinase protein function as intermediaries in signal trasduction
pathways resulting in the promotion of cellular growth. The encodes by? - Answersabl
and src proto-oncogenes
ABL1 is a protein that, in humans, is encoded by the ABL1 gene located on
chromosome 9. What is it pathology? - AnswersThe t(9;22) translocation results in the
f - Answers-
Bloom syndrome - predisposition to the development of cancer. AR inheritance. Carrier
frequency in Eastern European Jewish (Ashkenazi Jewish) ancestry - 1/100. The
mutations in the BLM gene inactivate the BLM protein's DNA helicase activity or nullify
protein expression. Lack of BLM protein or protein activity leads to an increase
mutations. List common characteristics of Bloom syndrome! - AnswersCommon
characteristics of Bloom syndrome - (1) short stature (2) rash develops early in life in
sun-exposed areas of the skin. (3) high-pitched voice (4) distinct facial features: narrow
face, micrognathism, prominent nose, ears (5) hypo- hyper-pigmented skin areas, cafe-
au-lait spots; (6) telangiectasias, also in the eyes (7) moderate immune deficiency - in
certain Ig - recurrent pneumonia, ear infections (8) hypogonadism - failure to produce
sperm, premature menopause
Fanconi anemia (FA) - genetic disease. Incidence of 1/350,000 births, with a higher
frequency in Ashkenazi Jews and Afrikaners in South Africa. FA is the result of a
genetic defect in a cluster of proteins responsible for DNA repair. As a result, the
majority of FA patients develop cancer - acute myelogenous leukemia, and 90%
develop bone marrow failure by age 40. 60-75% of FA patients have congenital defects,
commonly short stature, abnormalities of the skin, arms, head, eyes, kidneys, and ears,
and developmental disabilities. 75% of FA patients have some form of endocrine
problem, with varying degrees of severity. Median age of death 30 years. -
AnswersBecause of the genetic defect in DNA repair, cells from people with FA are
sensitive to drugs that treat cancer by DNA crosslinking, such
as mitomycin C. ~ 1,000 persons worldwide currently suffer from the disease. The
carrier frequency in the Ashkenazi Jewish - 1/90. There are 15 genes responsible for FA
- like breast-cancer susceptibility gene BRCA2. They are involved in the recognition and
repair of damaged DNA; genetic defects leave them unable to repair DNA.
ONCOGENES - AnswersONCOGENES
What is Proto-oncogenes? - AnswersProto-oncogenes are normal cellular proteins that
work to regulate normal growth and development. If mutated or misexpressed, the
proto-oncogenes become oncogenes and lead to aberrant cell cycle control.
What functon of Fibroblast growth factor (FSF)? - AnswersFibroblast growth factor
(FSFs) are family of proteins that are normally expressed during the proliferation of cells
required for normal wound healing, but overexpression can lead to tumor formation.
What functon of Platelet-derived growth factor (PDGF)? - AnswersPlatelet-derived
growth factor (PDGF) is a polypeptide that is normally important for extracellular matrix
production, but overexpression may results in proliferation as result of autocrine
stimulation.
Epidermal growth factor receptors (EGFRs): there are at least members of this family of
tyrosine kinase receptors, erb b-1, erb b-2, erb b-3 - AnswersWhen mutated, lead to
aberrant signaling and growth in the absence of the cognate ligand (EGF).
Overexpression of the growth factor receptor erb b-1, also known as HER2/neu, is
associated with development of breast cansers. Patients who overexpress HER2 in
their breast tumors can be treated with monoclonal antibody to HER2 which block
, signaling through this oncogenic pathway. Name this drug. - AnswersTrastuzumab
(Herceptin)
One of the mechanism of oncogenesis is Gene amplification defined as overexpression
of proto-oncogenes. GA can result from aberrant duplication of their DNA sequences,
often resulting in several hundred copies of the proto-oncogene and abnormal growth.
These duplicated regions can be seen on the chromosome as homogeneous staining
regions (HSRs). - AnswersBreast cancers are routinely screened for the presence of an
amplified HER2/neu oncogene. HER2/neu expression has been associated with a poor
prognosis. However, patients with HER2/neu overexpression are candidates for
Herceptin therapy.
What encodes RET proto-oncogene? - AnswersRET is a receptor tyrosine kinase for
members of the glial cell line-derived neurotrophic factor family (GDNF) of extracellular
signalling molecules or ligands (GFLs)
Loss of function mutations in RET prot-oncogene are associated with? - AnswersRET
loss of function mutations are associated with the development of Hirschsprung's
disease
Gain of function mutations in RET prot-oncogene are associated with the autonomous
growth promoting signals in the absence of ligand binding and development of various
types of human cancer, including? - AnswersParathyroid hyperplasia. Multiple
endocrine neoplasia (MEN) syndrome, including MEN I, which is charcterized by
Pancreatic, Pituitary, and Parathyroid tumors (PPP), and MEN II (A,B), which is
characterized by Adrenal (pheochromocytoma), Thyroid, and Parathyroid tumors (ATP),
also MEN IIC - familial medullary thyroid carcinoma (FMTC).
What encodes Ras (Rat sarcoma) proto-oncogene? - AnswersA GTP-binding protein
anchored to the inner cell membrane via a covalently attached farnesyl moiety.
In the inactive state, Ras binds GDP. In stimulation of the cell by growth factor-ligand
interactions, Ras exchanges GDP for GTP, leading to activation of downstream
signaling events. - AnswersThe Ras protein has intrinsic GTPase activity, terminating
the signal transduction events when GTP is hydrolyzed back to GDP, returning Ras to
its inactive state. Alterations in the Ras gene can change the Ras protein so that it is no
longer able to break up and release the GTP. These changes can cause the the
pathway to be stuck in the "on" position
The ras gene is the most commonly mutated oncogene in cancer, with 10-20% of
tumors harboring mutations in ras. - AnswersMutant ras has been identified in cancers
of many different origins, including: pancreas (90%), colon (50%), thyroid (50%), lung
(30%), bladder (6%), ovarian (15%), breast, skin, liver, kidney, and some leukemias. It
is also possible that in the future, ras may be used to detect certain cancers.
Historically, pancreatic cancer has been difficult to diagnose. The identification of ras
mutations in the DNA of pancreatic cells shed into feces may enable clinicians to
differentiate between chronic pancreatitis and pancreatic cancer.
Nonreceptor tyrosine kinase protein function as intermediaries in signal trasduction
pathways resulting in the promotion of cellular growth. The encodes by? - Answersabl
and src proto-oncogenes
ABL1 is a protein that, in humans, is encoded by the ABL1 gene located on
chromosome 9. What is it pathology? - AnswersThe t(9;22) translocation results in the
