title: Forty years of research on xeroderma pigmentosum at the US National Institutes of Health.
abstract: In 1968, Dr. James Cleaver reported defective DNA repair in cultured cells from patients with xeroderma pigmentosum. This link between clinical disease and molecular pathophysiology has sparked interest in understanding not only the clinical characteristics of sun sensitivity, damage and cancer that occurred in XP patients but also the mechanisms underlying the damage and repair. While affected patients are rare, their exaggerated UV damage provides a window into the workings of DNA repair. These studies have clarified the importance of a functioning DNA repair system to the maintenance of skin and neurologic health in the general population. Understanding the role of damage in causing cancer, neurologic degeneration, hearing loss and internal cancers provides an opportunity for prevention and treatment. Characterizing complementation groups pointed to the importance of different underlying genes. Studying differences in cancer age of onset and underlying molecular signatures in cancers occurring either in XP patients or the general population has led to insights into differences in carcinogenic mechanisms. The accelerated development of cancers in XP has been used as a model to discover new cancer chemopreventive agents. An astute insight can be a "tipping point" triggering decades of productive inquiry.
authors.affiliation: Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Kraemer
authors.forename: John J
authors.initials: JJ
authors.lastname: DiGiovanna
mesh_terms: D017668:Age of Onset; D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D004249:DNA Damage; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000235:genetics* / Q000378:metabolism; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D015474:Isotretinoin / Q000627:therapeutic use; D008545:Melanoma / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D009316:National Institutes of Health (U.S.) / Q000266:history*; D012867:Skin / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D014466:Ultraviolet Rays / Q000009:adverse effects; D014481:United States / Q000453:epidemiology; D014983:Xeroderma Pigmentosum / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*
chemical_list: D016588:Anticarcinogenic Agents; D004273:DNA, Neoplasm; D015474:Isotretinoin