p53 Analysis

The tumor suppressor gene p53, located on chromosome 17, is a key component of the body's anti-tumor defense. It functions in response to DNA damage that might otherwise lead to cancer. Normal p53 can arrest cell growth for DNA repair or send cells into the programmed cell death pathway (apoptosis). When p53 is mutated, its tumor suppressor effect may be lost. This can yield uncontrolled cell growth and may lead to cancer.

Mutations in p53 are associated with genomic instability and increased susceptibility to cancer. About 50% of the 1.3 million cancers diagnosed each year have p53 mutations. These mutations are found in both inherited and sporadic cancers. More than 51 types of human tumors with p53 mutations have been documented to date. Among common tumors, 90% of cervical, 70% of colorectal, 50% of lung and 20% of breast cancers carry p53 mutations. Germline p53 mutations can be inherited and occur frequently in cancer-prone families with Li-Fraumeni syndrome. Common cancers in these families include breast, soft tissue sarcomas and brain tumors.

Some studies show that p53 mutational status may also be predictive of tumor response to specific chemotherapeutics, radiation treatment or gene therapies. This is the case in breast cancer where initial studies have shown that cisplatin and Tamoxifen are more effective in patients whose tumors have a p53 mutation. Many disease-based drug trials employing molecular stratification are under way which may result in improved efficacy of traditional and gene-based anti-cancer therapeutics.