Chapter 8: Hereditary Risk Flashcards
Caretaker Genes
ATM
BLM
BRCA1 / BRCA2
XPA
Gain of Function Genes
RET
Familial Adenomatosis Polyposis (APC) Gene
Dominant
Colon Cancer
Gatekeeper
Familial Retinoblastoma (RB) Gene
Dominant
Retinoblastoma/Osteosarcoma
Gatekeeper
Li-Fraumeni syndrome (p53) Gene
Dominant
Various cancers
Gatekeeper
Ataxia Telangiectasia (ATM) Gene
Recessive
Lymphoma
Caretaker
Bloom Syndrome (BLM) Gene
Recessive
Multiple Cancers
Caretaker
Familial Breast Cancer (BRCA) Genes
Dominant
Breast/Ovary
Caretaker
Xeroderma Pigmentosum (XPA) Gene
Recessive
Skin
Caretaker
Multiple Endocrine Neoplasia (RET) Gene
Dominant
Thyroid
Gain of Function
Complete Penetrance
If inherited mutation is in a critical tumor suppressor gene, probability of developing cancer is 100%
Familial Cancers
Inherited
Penetrance of Gene
% of individuals with gene mutation that develop cancer
Incomplete Pentrance
Mutation in critical gene is inherited BUT ONLY 80-90% will develop cancer
RB gene
Tumor suppressor gene
Absence leads to cancer
Recessive
Two hit model
Retinoblastoma
Cancer of retinal nerve in children; can move along optic nerve to brain
Hereditary Retinoblastoma
Both eyes affected
1/3 cases
Heterozygous for mutation
Sporadic Retinoblastoma
One eye affected
2/3 of cases
RB Gene Mechanism
Acts like Mendelian dominant gene on chromosome 13
Normal function of RB gene (un-Phosphorylated )
Regulate cell division
Stops cells before S Phase (Restriction point) gene
Phosphorylated RB gene
Cells continue into S phase
Cdk-cyclins
Add phosphate to RB from birth to age 6
Two Hit Model
Mutation or Deletion are required
Single hit only disrupts one RB gene copy
In the retinoblastoma cell, what action is needed to transform the cell?
The absence of the protein is necessary
APC gene
Tumor suppressor gene
Two hit model
E-6 Viral Protein
Binds to p-53 gene in HPV
Tumor suppressor gene
Gatekeeper Function to stop cell proliferation
DNA repair enzyme
Caretaker function to repair DNA mistakes
Gain of function mutation
Oncogene protein is always active as a receptor on endocrine cells
Xeroderma Pigmentosum
Skin cancer caused by inherited defect in excision repair enzymes
“Camp Sundown”
Excision repair
Seven genes designated XPA - XPG code for required repair enzymes
XPV codes for
DNA polymerase for translesional repair of pyramidine diners
Mismatch repair
Repair that occurs during DNA replication
Inherited risk of breast cancer
Only 10% of all breast cancers show inheritance
Inheritance of mutated BRCA1 & BRCA2
40-80% risk breast cancer
15-65% risk ovarian cancer
Ataxia Telangiectasia
Dilation of capillaries and lack of coordination
40% risk of cancer
ATM Gene Function
Detect DNA damage (by radiation) and sending signal to p-53
BLM Gene Function
Codes for DNA helicase to unwind DNA in repair
Primary immune deficiencies
Lack of thymus, etc.
Induced Immune Deficiencies
HIV
Immune deficiency
Mostly leads to lymphomas and leukemias often by EBV
Gatekeeper Genes
APC
RB
p53
