Tumor suppressor genes Flashcards
RB
Syndrome: Retinablastoma
Major tumor: Retinablastoma, osteosarcoma
TP53
Syndrome: Li-Fraumeni Syndrome
Major tumor: Soft-tissue sarcoma, glioma, leukemia
APC
Syndrome: Familial adenomatous polyposis (FAP)
Major tumor: Colorectal Cancer
MSH2,MLH1,PMS1/2
Syndrome: Hereditary nonpolyposis colon cancer (HNPCC)
Major tumor: colorectal cancer
BRCA1/2
Syndrome: Familial Breast/ovarian cancer
Major tumor: Breast and ovarian cancer
VHL
Syndrome: Bon Hippel-Lindau Syndrome
Major tumor: Hemangioblastoma, pheochromocytoma, renal cell carcinoma
NF1
Syndrome: Neurofibromatosis type 1
Major tumor: Neurofibroma , astrocytoma, sarcoma, leukemia
NF2
Syndrome: Neurofibromatosis type 2
Major tumor: Schwannoma, meningioma, ependymoma
TSC1/2
Syndrome: Tuberous sclerosis complex
Major tumor: cortical dysplasia, renal angiomyolipoma
WT1
Syndrome: WAGR (Wilms Tumor, aniridia, Genitourinary anomalies, growth retardation)
Major tumor: wilms tumor
MEN1
Syndrome: Multiple Endocrine Neoplasia 1
Major tumor: Islet Cell adenoma, pituitary adenoma, parathyroid adenoma
Wilms tumor
Autosomal dominant inheritance
results from the loss of function in the WT1 gene on chromosome 11 which encodes a transcription factor important in the control of cell growth and differentiation
Two hit hypothesis: sporadic cancers
“two hits”(mutations) are needed for tumor progression
A mutation occurs in a tumor suppressor gene on one homolog in one cell
the second mutation occurs in the same gene(2nd copy) in the same cell
leads to loss of all tumor suppressor activity
Two hit hypothesis Familial cancers
The 1st hit is present in every cell inherited. only one more hit needed for tumor initiation
Mechanisms producing the 2nd hit
non disjunction
mitotic recombination
gene deletion
point mutation
what are the genes needed for regulation of the G1-S checkpoint
RB
CDK4,
Cyclin D gene
CDKN2A
What is this image of?
White pupillary reflex in the eye
indicative of retinoblastoma
What happens if there is loss of function of the p53 protein?
net cell growth
increased mutation frequency
what are the differences between familial and sporadic cancer forms?
Take some time to think about it
Familial/mendelian
- Germline mutation
- Multiple tumors
- bilateral
- early onset
Sporadic
- starts with normal gene
- single tumor
- unilateral
- later onset
Li-Fraumeni Syndrome
Inherited mutation of p53
Increases risk of cancer at young age
several types of cancer
1st hit is maternally inherited, 2nd hit is somatic
Familial Adenomatous Polyposis
Autosomal dominant inheritance
Affects Beta catenin involved in growth control pathway
Allows Beta catenin to not be degraded and grown in the absence of the WNT signal
