Alpha-fetoprotein (AFP) and Chromosomal/Genetic Instability Disorders: Is AFP a Reporter Protein for DNA Damage-Sensing and Repair?

Many cancer cells exhibit an unstable genome resulting from chromosomal aberrations and gene mutations in somatic cells which generate heterogeneous cell populations manifesting diseases such as cancer. Genomic/chromosomal instability can arise from non-repaired broken DNA along the chromosome or from loss of telomeric ends of chromosomes. Normally, DNA single or double-stranded breaks are repaired prior to the cells’ entrance into the mitotic phase of the cell cycle. This progressive passage is overseen by DNA-damage sensors, checkpoint proteins, and kinase enzymes at each cyclic phase transition point. However, some cancer cells exhibit escape behaviors to evade checkpoint surveillance networks during cell cycle progression. Examples of human diseases associated with DNA-associated disorders can be found in ataxia telangiectasia (AT), Fanconi’s anemia (FA), immunodeficiency disorders, and others. Serum alpha-fetoprotein (AFP) levels have been reported as abnormal in these and other DNA/ chromosome instability disorders; in such situations, AFP appears to reflect the presence of impaired DNA damage and repair networks in certain cells. Although serum AFP presently serves as a biomarker in multiple disorders and diseases such as liver cancer and teratomas, the present discourse suggests that AFP might further serve as a reporter protein for the presence of DNA-damage sensing and repair networks in precancerous transforming cells.