Justin's genetics Flashcards
Cancer of which of the following disease sites is least likely to be associated with BRCA2?
a) Small bowel
b) Biliary
c) GU
d) breast
e) ovarian
f) colon
Colon
Which is not associated with breast cancer?
A. Li Fraumeni
B. MEN2
C. Cowden
D. Ataxia telangiectasia
B. MEN2 (multiple endocrine neoplasia)
Which gene is not breast cancer risk related?
a) APC
b) PTEN
c) p53
APC
What is methylation
Epigenetic change. methylation of cytosine residues residing next to guanine residues (CpG dinucleotides). methylation silences gene expression. not a SNP
What happens with a TP53 mutation?
(Duplicate Q x3)
Misense mutation in one copy of the TP53 gene results in full length proteins, unable to bind DNA and regulate transcription of other genes
Mutation of one TP53 gene often accompanied by deletion of the other copy; leaves the cancer cell with only mutant P53 protein
Even if cancer still retains one normal copy of TP53 gene, mutant P53 protein complexes with wild type P53 protein and inactivates it, functioning in dominant negative fashion
Over accumulation of mutant P53 protein is detected via IHC
Type 2 endometrial cancer (and pap serous ovarian cancer) associated with what mutations?
a) p53 & Her2
b) MLH & p53
c) PMS2 & Her2
a) p53 & Her2
Screening for HNPCC
-Risk of colon cancer
-Screening guidelines for CRC
**TEST QUESTION **
50-80% risk
Colonoscopy between ages 20-25 or 2-5 years before youngest dx in family, every 1-2 yrs
20-25 for HNPCC genes MLH1, MSH2/EPCAM
30-35 for PMS2/MSH6
….or 2-5yr prior to earliest familial CRC
HNPCC screening guidelines for endometrial cancer and risk
**TEST QUESTION **
Risk - 16-60%
No evidence for EMB or US, can consider/discuss as well as TAH/BSO after childbearing
HNPCC screening for stomach/small bowel
**TEST QUESTION **
EGD every 2-4 years starting age 30-40 for all mutations. Also H.pylori testing/treating (7/23 NCCN)
Rhyming
30 to 40. H. Pylori
HNPCC screening for
-urothelial
-pancreatic
-CNS
**TEST QUESTION **
Urothelial: consider annual UA starting age 30-35
Pancreatic- consider annual contrast-enhanced MRI/MRCP and/or EUS, starting age 50 if there is a family history (all genes except PMS2)
CNS-none
updated NCCN 7/23
Peutz Jeghers germline mutation
(Duplicate)
STK11
Chromosome 19p13
Peutz Jeghers :
What is the clinical picture?
What cancers are they at risk for?
Increase gyn related issues?
(Duplicate)
Clinical picture: GI polyps, pigmented lesions on lips/mouth
Cancer risk: GI and breast cancer
Gyn issues: SCTAT (sex cord tumors with annular tubules of ovary) and adenoma malignum of the cervix
PPP SCAT SCRAM! (Like telling a cat to scram)
PPP: Peutz Polyps Pigmented
SCtAT and sCrAM: (Cervical adenoma malignum)
Peutz Jeghers – which screening test is not needed?
a) colnoscopy
b) paps
c) US
d) EMB
e) breast imaging
EMB
Annual pelvix exam and US (for ovaries). EMBx if AUB (per NCCN 2023)
What is the normal function of the P53 protein?
P53 protein resides in the nucleus and exerts tumor suppressor activity by binding to transcriptional regulatory elements of genes such as CDK inhibitor P21 that arrest cells in G1
Most common germline ov ca mutation
A p53
B BRCA 1
C BRCA 2
D MLH1
BRCA 1
