5.4 Familial Cancer Flashcards
What are the types of mutations that can arise to cause cancer?
Acquired - somatic
Inherited - Germline
What are the genes usually involved in cancer?
Mutated or activated oncogenes
Loss or mutated tumour suppressor genes
DNA repair genes
How do oncogenes cause cancer?
1 mutation which causes accelerated cell division
What is the oncogene over expressed in colon cancer?
RAS and C-MYC
What is the oncogene over expressed in hereditary papillary renal cancer?
MET
What is the oncogene over expressed in familial melanoma cancer?
CDK4
What is the oncogene over expressed in CML cancer?
BCL/ABL
What is the two hit hypothesis?
1 mutation causes the carrier to be susceptible and the 2nd mutation or loss causes cancer
What type of gene is associated with familial cancer syndrome?
Tumour suppressor genes
What are the clinical features suggestive of familial/inherited susceptibility?
Occurs at young age
Multiple tumours in single organ or bilateral paired
More than 1 primary
Family history or same type or related type
High rate in family
What is the gene associated with retinoblastoma?
RB1 gene on chromosome 13
What are the features of retinoblastoma?
Unilateral until 26 months, bilateral 8 months
Familial likely to be bilateral younger
What type of genes are BRCA 1 and 2 and what is their inheritance)
Tumour suppressor genes (autosomal dominant)
Where are BRCA 1 and 2 located?
1: chromosome 17
2: chromosome 13
How do tumours in BRCA 1 and 2 carriers occur?
Need to have inactivation of both alleles, one inactivated as a result of inherited germline mutation and the second is acquired (somatic inactivation)
What are the pathologic features of BRCA 1 and 2 breast cancer?
1: triple negative, high grade occurring in young women
2: ER+ and may occur late
What are the management options for BRCA carriers?
Cancer screening
Prophylactic mastectomy
Prophylactic salpingo-oophrectomy
Which gene is associated with increase risk of Male breast cancer?
BRCA2
What is category 1 gene mutations and give examples
Highly penetrant genes with will recognised syndromes
BRCA 1/2, p53, CDH1, STK11, MMR
What needs to be considered with genetic screening?
Need to give counselling and it is hard to know what to do with category 2/3 results
What is TP53 mutation associated with?
Li-Fraumeni
What is PTEN mutation associated with?
Cowden/PTEN hamartoma
What is STK11 mutation associated with?
Peutz-Jeghers
What is MMR gene mutations associated with?
Lynch (HNPCC)
What is the difference between tumour suppressor genes and DNA repair genes?
TSG are directly involved in growth inhibition or differentiation while DNA repair genes are indirectly involved
What usually occurs as a result of inactivation of DNA repair genes?
Increased rates of mutation in other cellular genes including proto-oncogenes and tumour suppressor genes
What are the examples of DNA repair genes?
Neucleotide excision repair, mismatch repair and somatic mutational disorders
How does Neuleotide excision repair work and what disorder results from muatation?
repairs helix-istorting chemical adducts especially UV light
Xeroderma Pigmentosa
What results from germline mutations in MMR genes and what are the genes?
HNPCC (Lynch syndrome) - typically right sided/proximal colon cancer
MSH2, MLH1, MSH6 (PMS1, PMS2)
What other cancers are associated with the MMR germline mutations?
Colorectal, Endometrial, Gastric, Ovarian, Biliary tract, Urinary tract, Small bowel, Brain/CNS
What are the two (3) most common genes that are lost in HNPCC?
MSH2 and MSH6 the most common
MHL1 can also occur in sporadic CRC
