Common Hereditary cancer syndromes

Syndrome Gene Associated neoplasms Pathogenesis

MSH2, MLH1, MSH6,  Colorectal cancer
Lynch syndrome PMS2 (mismatch  Endometrial cancer
repair mutation)  Ovarian cancer
 Colorectal cancer
Familial adenomatous
APC  Desmoids and osteomes
polyposis
 Brain tumors
Autosomal dominant.
 Hemangioblastomas
Caused by inactivating
Von Hippel-Lindau VHL  Clear cell renal carcinoma
mutation in corresponding
 Phechromocytoma supressor gene.
Deletion of remaining
 Sarcomas normal allele (second hit)
 Breast cancer leads to heterozygosity and
Li-Fraumeni Syndrome p53  Brain tumors malignant transformation
 Adrenocortical carcinoma
 Leukemia

 Parathyroid adenomas
Multiple endocrine
MEN1  Pituitary adenomas
neoplasia type 1
 Pancreatic adenomas

Autosomal dominant.
Activating (gain of function)
 Medullary thyroid cancer
point mutation in
Multiple endocrine RET (Neural growth  Pheochromocytoma
proto-oncogen.
neoplasia type 2 factor receptor)  Parathyroid hyperplasia
Continuous stimulation of
(MEN2A)
cell division predisposes
tumor growth

GF / Suppressor Type Mutation Cancer

PDGFB Platelet-derived Growth factor B Overexpression Astrocytoma

EEBB2 (HER2 neu) Epidermal growth factor receptor Amplification Subset of breast carcinomas
KIT Stem cell growth factor receptor Point mutation Gastrointestinal stromal tumor
RAS gene GTP-binding protein Point mutation Carcinomas, melanoma and
lymphoma
ABL Tyrosine kinase t(9:22) with BCR CML and some types of ALL
Overexpression
c-MYC Transcription factor t(8:14) involving IgH Burkitt lymphoma
N-MYC Amplification Neuroblastoma
L-MYC Amplification Lung carcinoma (Small cell)
CCND1 Cyclin t(11:14) involving IgH Mantle B-cell lymphoma
CDK4 Cyclin-dependent kinase Amplification Melanoma
BCL2 Regulator of Apoptosis t(14:18) involving IgH Follicular lymphoma
Overexpression