Hereditary Cancer Syndromes Flashcards
MYC
Burkitt lymphoma, lung and breast cancer
BRAF
melanoma
GLI1
basal cell carcinoma
K-RAS
melanoma
N-MYC
neuroblastoma
ABL
chronic myeloid leukemia
Series of Events in Colon Cancer
- Loss/mutation of APC gene
- DNA hypomethylation activates KRAS oncogene
- LOH @ 18q with loss of SMAD4
- final loss or mutation of p53
Retinoblastoma
Rb gene on Chromosome 13 is tumor supppressor
Rb gene inhibits proliferation, differentiation, apoptosis
Rb is LOST
Von Hippel Lindau
autosomal dominant, spectrum of tumors
hemangioblastomas - brain, SC, retina
renal cysts & clear cell renal carcinoma; pheochromocytoma
endolymphatic sac tumors
mTOR key facilitator of tumor genesis, signal to control it knocked out in VHL
HNPCC
5% autosomal dominant, 80% penetrance multiple primary tumors heterogenity- different genes mutated proximal colon tumor site; extracolonic DNA Testing: MSI- microsatellite instability; nuc repeats in normal tissue vs. tumor tissue; compare
FAP 1%
mutations in APC gene (tumor suppressor)
truncation of protein
hotspot at codon 1309
autosomal dominant
Hereditary Breast/Ovarian
BRCA 1 or 2
private mutations specific to family
BRCA 1 Mut: 65%
BRCA 2 Mut: 45%
Li-Fraumeni
spectrum of tumors: breast, brain, acute leukemia, soft tissue and bone sarcomas
1. Proband diagnosed with sarcoma at age less than 45
2. Primary relative any cancer less than 45 or sarcoma at any age
p53 = 85-90%
CHK2 = more breast
Cri Du Chat
deletion in 5p15.2
Point Mutation Examples
PTEN (ovarian)
Src
Amplification Examples
cMYC-max
Her2
N-myc
Traslocation examples
Burkitt’s t8:14
IgH and & MYC
CML
uncontrolled receptor tyrosine kinase, use Gleevec. fuses BCR and Abi
