Tumor suppressor are genes that normally 

prevent cells from becoming cancerous. 

A loss of function in both alleles significantly increases the risk for cancer.
Mutation in adenomatous polyposis coli or APC gene located on chromosome 5q is
associated with colorectal cancers, especially those occurring in patients with familial
adenomatous polyposis (FAP).
BRCA1, located on chromosome 17q, is associated with
hereditary breast cancerand ovarian cancer. The gene normally plays a role in repairing
chromosomal damage and double-stranded DNA breaks.
Individuals with BRCA2 mutations have an increased risk of the following malignancies:
 Breast cancer (including male breast cancer)

 Ovarian cancer

 Pancreatic cancer

 Prostate cancer

The gene product, like BRCA1, plays a role in DNA repair.

Deletion in DPC4/SMAD4, which is located on chromosome 18q, is associated
with pancreatic cancer.  Mnemonic: DPC = “Deleted in Pancreatic Cancer”.
The Deleted in Colorectal Carcinoma, or DCC gene, is located on chromosome 18q and
is associated with colon cancer.
The multiple endocrine neoplasia 1, or MEN1 gene, is located on chromosome11q and
encodes the tumor suppressor protein known as menin. It is associated with MEN type 1
syndrome which is characterized by abnormalities in the parathyroid, pancreas and
pituitary glands.  
The neurofibromin 1, or NF1 gene, located on chromosome 17q, is associated
with RAS GTPase activation and is mutated in neurofibromatosis type 1. 
The neurofibromin 2, or NF2, located on chromosome 22q, codes for a cytoskeletal
protein, merlin, and is associated in neurofibromatosis type 2. 
The P16 gene, which is located on chromosome 9p, is a cyclin-dependent kinase
inhibitor and is associated with melanoma.
The P53 gene, located on chromosome 17p, regulates cell cycle progression from the G1
to S phase and is involved in most human cancers. Li-Fraumeni syndrome is autosomal
dominant cancer syndrome caused by germline mutation of the p53 gene, characterized
by an increased risk for developing sarcomas, leukemias, and cancers of the breast, brain,
and adrenal glands at young age.
Loss-of function mutations in the PTEN tumor suppressor gene is associated with:
 Breast cancer

 Prostate cancer

 Endometrial cancer

 Cowden Syndrome (autosomal dominant disorder in which a

hereditary PTEN mutation predisposes patients to breast cancer, follicular thyroid
carcinoma, endometrial carcinoma, as well as benign skin tumors and GI
hamartomas).

PTEN encodes a tumor suppressor protein that acts as phosphatase to dephosphorylate

PIP3, thereby inhibiting downstream AKT (aka protein kinase B) activation.
Retinoblastoma, or Rb gene, located on chromosome 13q, blocks the G1 to S phase
progression and is associated with retinoblastoma and osteosarcoma.
The TSC1 gene, located on chromosome 9q, codes for the tumor suppressor
protein hamartin and is associated with tuberous sclerosis. This disease is associated
with numerous benign, hamartomatous neoplasms, including
 Angiofibromas of the skin

 Angiomyolipomas of the kidney

 Rhabdomyomas of the heart

 Subependymal giant cell astrocytoma of the brain

The TSC2 gene, located on chromosome 16, codes for the tuberin protein and is
associated with tuberous sclerosis. This disease is associated with numerous benign,
hamartomatous neoplasms, including
 Angiofibromas of the skin

 Angiomyolipomas of the kidney

 Rhabdomyomas of the heart

 Subependymal giant cell astrocytoma of the brain.

The von Hippel-Lindau (VHL) gene, located on chromosome 3p, normally acts to inhibit

hypoxia inducible factor (HIF) 1a. Loss of VHL results in constitutive expression of HIF
and excess activation of angiogenic growth factors, resulting in von Hippel-Lindau
disease. Neoplasms common to this disease include
 Renal cell carcinoma (often bilateral)

 Hemangioblastoma (of the retina, cerebellum, and brain stem)

 Pheochromocytoma

 Cavernous hemangiomas of the skin, mucosa, or organs

Wilms tumor proteins, WT1 and WT2, located on chromosome 11p, are associated

with Wilms tumor (nephroblastoma) in children.

CDKN2A is most commonly mutated in melanoma and pancreatic cancer.

CDKN2A encodes p16, which blocks the G1 to S phase transition in the cell cycle.