Cancer genetics Exam QUESTIONS WITH
COMPLETE SOLUTIONS (ANSWERS VERIFIED 100%
CORRECT)
Tumor Suppressor Genes - ✔✔Normally block uncontrolled cellular proliferation
Therefore, suppress tumor formation
Usually involved in regulating cell cycle
Recessive at the cellular level
Require two copies of mutant allele to form tumor
Somatic (non-tumor) cells will still be heterozygous
Proto-oncogenes - ✔✔Produce 4 basic regulators of cell growth
Growth factors
Growth factor receptors
Signal transduction molecules
Nuclear transcription factors
Mutation in proto-oncogene Oncogene
Unregulated cell growth and differentiation
Dominant at the cellular level -gain-of-function mutation
Very rarely present in the germline
Senescence - ✔✔Telomeres at ends of chromosomes shorten with each cell division
After 50 -70 cell mitotic events, telomeres depleted -->senescence-->apoptosis
Tumor cells activate gene for telomerase
Adds telomeres to newly divided cells
,Allows for continued cell division
Rarely found in normal cells
Telomerase present in up to 90% of tumor cells
TP53 - ✔✔-Mutations in TP53occur in > half of all human tumor types (>50 types
isolated so far)
-TP53codes for p53
-1st function of p53: Halt cell cycle for DNA repair to occur prior to S phase
2ndFunction of p53: - ✔✔-Induce apoptosis if DNA damage is beyond repair
-If problems with normal function of pRbpathway of repair, then apoptosis induced by
p53
If problems with TP53(i.e. mutation): - ✔✔-Can not repair damage prior to replication
-Can not induce apoptosis of cells with DNA damag
TP53 and Clinical Prognosis - ✔✔Tumor tissue analysis to determine prognosis
TP53mutations carry particularly poor prognosis
Associated with aggressive form of cancer
Therapeutic potential
Insertion of "normal" TP53into tumors with TP53mutation
Induces apoptosis in transfectedcells
Results in tumor regression
Fraught with typical problems of gene therapy
, TP53and Li FraumeniSyndrome (LFS) - ✔✔Autosomal dominant (at the
organismallevel)
Early onset
½ develop invasive cancer by age 30
90% have primary tumor by age 70
Often multiple primary tumors
Breast, Colon, Soft tissue sarcoma, Osteosarcoma, Brain tumors, Leukemia,
Adrenocorticalcarcinoma
75% have mutations in p53 (two-hit model)
Remainder have mutation in CHEK2which activates p53
TP53 and Toxins - ✔✔AflatoxinB1
Present in Aspergillussp.
Found in mold contaminated grains
Small quantities innocuous
Persistent exposure Liver cancer
Benzopyrene
Found in cigarette smoke
Persistent exposure Lung cancer
Specific mutagens cause specific TP53mutations
Analyze tumor tissue for mutation type
Retrospective determination of mutagen
TP53and Infectious Agents TP53 and Infectious Agents (HPV) - ✔✔Human Papilloma
Virus (HPV)
DNA tumor virus
COMPLETE SOLUTIONS (ANSWERS VERIFIED 100%
CORRECT)
Tumor Suppressor Genes - ✔✔Normally block uncontrolled cellular proliferation
Therefore, suppress tumor formation
Usually involved in regulating cell cycle
Recessive at the cellular level
Require two copies of mutant allele to form tumor
Somatic (non-tumor) cells will still be heterozygous
Proto-oncogenes - ✔✔Produce 4 basic regulators of cell growth
Growth factors
Growth factor receptors
Signal transduction molecules
Nuclear transcription factors
Mutation in proto-oncogene Oncogene
Unregulated cell growth and differentiation
Dominant at the cellular level -gain-of-function mutation
Very rarely present in the germline
Senescence - ✔✔Telomeres at ends of chromosomes shorten with each cell division
After 50 -70 cell mitotic events, telomeres depleted -->senescence-->apoptosis
Tumor cells activate gene for telomerase
Adds telomeres to newly divided cells
,Allows for continued cell division
Rarely found in normal cells
Telomerase present in up to 90% of tumor cells
TP53 - ✔✔-Mutations in TP53occur in > half of all human tumor types (>50 types
isolated so far)
-TP53codes for p53
-1st function of p53: Halt cell cycle for DNA repair to occur prior to S phase
2ndFunction of p53: - ✔✔-Induce apoptosis if DNA damage is beyond repair
-If problems with normal function of pRbpathway of repair, then apoptosis induced by
p53
If problems with TP53(i.e. mutation): - ✔✔-Can not repair damage prior to replication
-Can not induce apoptosis of cells with DNA damag
TP53 and Clinical Prognosis - ✔✔Tumor tissue analysis to determine prognosis
TP53mutations carry particularly poor prognosis
Associated with aggressive form of cancer
Therapeutic potential
Insertion of "normal" TP53into tumors with TP53mutation
Induces apoptosis in transfectedcells
Results in tumor regression
Fraught with typical problems of gene therapy
, TP53and Li FraumeniSyndrome (LFS) - ✔✔Autosomal dominant (at the
organismallevel)
Early onset
½ develop invasive cancer by age 30
90% have primary tumor by age 70
Often multiple primary tumors
Breast, Colon, Soft tissue sarcoma, Osteosarcoma, Brain tumors, Leukemia,
Adrenocorticalcarcinoma
75% have mutations in p53 (two-hit model)
Remainder have mutation in CHEK2which activates p53
TP53 and Toxins - ✔✔AflatoxinB1
Present in Aspergillussp.
Found in mold contaminated grains
Small quantities innocuous
Persistent exposure Liver cancer
Benzopyrene
Found in cigarette smoke
Persistent exposure Lung cancer
Specific mutagens cause specific TP53mutations
Analyze tumor tissue for mutation type
Retrospective determination of mutagen
TP53and Infectious Agents TP53 and Infectious Agents (HPV) - ✔✔Human Papilloma
Virus (HPV)
DNA tumor virus
