Alpha-fetoprotein and Fanconi Anemia: Relevance to DNA Repair and Breast Cancer Susceptibility.
Elevations of serum alpha-fetoprotein (sAFP) have been reported in fetal and infant states of anemia. Fanconi anemia (FA) belongs to a family of genetic instability disorders which lack the capability to repair DNA breaks. The lesion occurs at a checkpoint regulatory step of the G2 to mitotic transition, allowing FA cells to override cell-cycle arrest. FA DNA repair pathways contain complementation groups known as FANC proteins. FANC proteins form multi-protein complexes with BRCA proteins and are involved in homologous DNA repair. An impaired cascade in these events imparts an increased breast cancer susceptibility to female FA patients. Elevations of sAFP have availed this fetal protein to serve as a biomarker for FA disease. However, the origin of the synthesis of sAFA has not been determined in FA patients. We hypothesize that hematopoietic multipotent progenitor stem cells in the bone marrow are the source of sAFP production in FA patients.
a Department of Obstetrics and Gynecology , Richmond University Medical Center , Staten Island , New York , USA.
Nisha A
NA
Lakhi
b Wadsworth Center , New York State Department of Health , Albany , New York , USA.
Gerald J
GJ
Mizejewski
D000293:Adolescent; D000328:Adult; D024682:BRCA2 Protein / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics*; D002453:Cell Cycle; D002648:Child; D002675:Child, Preschool; D002875:Chromosomes / Q000648:ultrastructure; D004260:DNA Repair; D005199:Fanconi Anemia / Q000235:genetics* / Q000378:metabolism; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005816:Genetic Complementation Test; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D013234:Stem Cells / Q000166:cytology; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000235:genetics / Q000378:metabolism*
C097353:AFP protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D015415:Biomarkers; D051856:Fanconi Anemia Complementation Group Proteins; D000509:alpha-Fetoproteins
Alpha-fetoprotein; DNA repair; Fanconi anemia; bone marrow; breast cancer; cell cycle; chromosome instability; stem cells