Familial Cancer Flashcards
How do genetic alterations arise for most cancers?
exposure to environmental carcinogens (not inherited)
What proteins are generally involved in genetic alterations in cancers?
- tumour suppressor genes
- oncogenes
What are tumour suppressor genes and proto-oncogenes involved with normally?
The control of cellular growth and proliferation
What are stability genes?
Group of cancer genes involved in DNA repair mechanisms (e.g. MLH1)
Do mutations in stability genes cause a gain or loss of function?
Loss in function
What protective cellular mechanisms can cancers overcome?
- Apoptosis
- Replicative senescence
What is replicative senescence?
The irreversible cell cycle arrest that is responsible for the limited number of cell divisions achievable by non-stem cells
What is the most common inheritance pattern for familial cancers?
autosomal dominant with incomplete penetrance
List functions of tumour suppressor genes
- negatively regulate cell-cycle progression
- promote apoptosis
- play a role in cell adhesion
Do mutations in tumour suppressor genes cause a gain or loss of function?
loss in function
TSG alterations may be due to:
- missence mutation affecting a functionally important amino acid
- a nucleotide sequence change affecting splicing
- a protein truncating mutation
- methylation of cytosines in CpG dinucleotides around the promoter (causing transcriptional repression or silencing
- gene deletions
What is the TP53 gene responsible for?
Encoding p53
What is the role of p53?
important role in pathways triggering cell-cycle arrest and apoptosis
Envionmental mutagens that cause defects in DNA repair systems can lead to which cancers?
- MUTYH associated polyposis
- BRCA1/BRCA2 related familial breast/ovarian cancer
What is the role of BRCA1/2
The accurate repair of double stranded breaks, such as those resulting from ionisation radiation or radiomimetric chemicals
What is the result of defective BRCA1/2?
mutations or large scale genomic instability
Which genes are associated with defects in accidental base incorporations at time of DNA replication and what would their products normally do?
- MSH2
- MLH1
- PMS1
- PMS2
interact to effect mismatch repair
Do mutations in oncogenes cause a gain or loss of function?
gain function, or overactivity
What is the result of an alteration of one oncogene?
Confers tumorigenic effect on the cell
Are TSGs or oncogenes more commonly responsible for tumour susceptibility syndromes?
TSGs
Give examples of oncogene associated familial cancers
- RET associated with multiple endocrine neoplasia
- MET associated with hereditary papillary renal cell carcinoma
What gene mutations are commonly associated with familial breast and ovarian cancer?
- BRCA1
- BRCA2
What are the rarer causes of familial breast and ovarian cancer?
- Li Fraumeni syndrome
- Cowden disease (PTEN)
- Peutz-Jeghers syndrome (STKII)
What features would make you suspect inherited breast cancer?
- early age of onset
- bilateral disease
- coexistant ovarian cancer
- family history of breast or ovarian cancer
