Examples of Inherited Predisposition to Cancer
Gene
Inherited predisposition
Inherited cancer syndromes (AD)
RB
Retinoblastoma
p53
Li-Fraumeni syndrome (various tumors)
p16/INK4A
Melanoma
APC
Familial adenomatous polyposis/colon cancer
NF1, NF2
Neurofibromatosis 1 and 2
BRCA1, BRCA2
Breast and ovarian tumors
MEN1, RET
Multiple endocrine neoplasia 1 and 2
MSH2, MLH1, MSH6
Hereditary nonpolyposis colon cancer
PTCH
Nevoid basal cell carcinoma syndrome
PTEN
Cowden syndrome (epithelial cancers)
LKB1
Peutz-Jegher syndrome (epithelial cancers)
VHL
Renal cell carcinomas
Inherited syndromes of defective DNA repair (AR)
Xeroderma pigmentosum
Ataxia-telangiectasia
Bloom syndrome
Fanconi anemia
Familial cancers
Familial clustering of cases, but role of inherited predisposition not clear for each individual
Breast cancer
Ovarian cancer
Pancreatic cancer
Selected oncogenes, their modes of activation, and associated human tumors
Category
Protooncogene
Mode of activation
Growth factors
PDGF-β chain
SIS (PBGFB)
Overexpression
Fibroblast growth factors
HST1
INT2 (FGF3)
Overexpression
Amplification
TGF-α
TGFA
Overexpression
HGF
Growth factor receptors
EGF-receptor family
FMS-like tyrosine kinase 3
Receptor for neurotrophic
factors
HGF
Overexpression
ERBB1 (EGFR), ERRB2
FLT3
RET
Overexpression
Amplification
Point mutation
Point mutation
Associated human tumor
Astrocytoma
Osteosarcoma
Stomach CA
Bladder CA
Breast CA
Melanoma
Astrocytomas
Hepatocellular carcinomas
Thyroid CA
Squamous cell carcinoma of lung, gliomas
Breast and ovarian CA
Leukemia
MEN2A and B, familial medullary thyroid
carcinomas
Gliomas, leukemias
GI stromal tumors, seminomas, leukemias
PDGF receptor
PDGFRB
Receptor for stem cell (steel) KIT
factor
Proteins involved in signal transduction
GTP-binding
KRAS
HRAS
NRAS
Nonreceptor tyrosine kinase
ABL
Overexpression, translocation
Point mutation
RAS signal transduction
WNT signal transduction
BRAF
β-catenin
Point mutation
Point mutation
Overexpression
C-MYC
N-MYC
L-MYC
Translocation
Amplification
Amplification
Burkitt lymphoma
Neuroblastoma, small-cell carcinoma of lung
Small-cell carcinoma of lung
Cell cycle regulators
Cyclins
Cyclin D
Cyclin dependent kinase
Cyclin E
CDK4
Translocation
Amplification
Overexpression
Amplification or point mutation
Mantle cell lymphoma
Breast and esophageal cancers
Breast cancer
Glioblastoma, melanoma, sarcoma
Nuclear-regulatory proteins
Transcriptional activators
Point mutation
Point mutation
Point mutation
Translocation
Colon, lung, pancreatic tumors
Bladder and kidney tumors
Melanomas, hematologic malignancies
Chronic myeloid leukemia
Acute lymphoblastic leukemia
Melanomas
Hepatoblastomas, Hepatocellular carcinoma
Selected tumor suppressor genes involved in human neoplasms
Subcellular location Gene
Function
Cell surface
Inner aspect of
plasma membrane
TGF-β receptor
E-cadherin
NF-1
Cytoskeleton
NF-2
Cytosol
APC/β-catenin
Nucleus
PTEN
SMAD2 & 4
RB
p53
Growth inhibition
Cell adhesion
Inhibition of RAS signal
transduction and of p21
cell-cycle inhibitor
Cytoskeletal stability
Inhibition of signal
transduction
PI-3 kinase signal transduction
TGF-β signal transduction
Regulation of cell cycle
BRCA1 & 2
Cell-cycle arrest &
apoptosis in response to
DNA damage
Nuclear txn
Regulation of cell cycle by
inhibition of cyclindependent kinases
DNA repair
KLF6
Txn factor
WT-1
p16 (INK4a)
Tumors assoc. w/ somatic
mutations
Carcinomas of colon
Carcinoma of stomach
Neuroblastomas
Tumors assoc. w/ inherited
mutations
Unknown
Familial gastric CA
Neurofibromatosis type 1 and
sarcomas
Schwannomas and meningiomas
Neurofibromatosis type 2,
acoustic schwannomas and
meningiomas
Familial adenomatous
polyposis coli/colon cancer
Unknown
Unknown
Retinoblastomas, osteosarcoma
Carcinomas of stomach, colon,
pancreas; melanoma
Endometrial and prostate cancers
Colon, pancreas tumors
Retinoblastoma; osteosarcoma
carcinomas of breast, colon, lung
Most human cancers
Wilms tumor
Pancreatic, breast, and esophageal
cancers
Unknown
Carcinomas of female breast
and ovary; carcinomas of
male breast
Unknown
Prostate
[More boxes to add from BioChem etc…]
Gene
Function
Li-Fraumeni syndrome;
multiple carcinomas &
sarcomas
Wilms tumor
Malignant melanoma
Tumors assoc.