The laboratory is studying molecular, cellular and clinical abnormalities in human cancer-prone genetic diseases. Current studies are focusing on xeroderma pigmentosum (XP) a cancer-prone genetic disease with cellular hypersensitivity to environmental agents and trichothiodystrophy (TTD) a genetic disease with similar cellular hypersensitivity but no increase in cancer risk. We identified several unusual XP patients. We found that mutations in the splice lariat branch point sequence of the XPC gene result in either severe or mild clinical symptoms depending on the amount of normal XPC mRNA produced. We found that normal appearing parents of XPC patients have markedly reduced levels of XPC mRNA. We identified new patients with mutations in the XPB helicase, a protein that is essential for life and is involved in transcription and DNA repair. These patients had severe or mild disease depending on their mutations. In a collaborative study we found that the frequency of an XPA founder mutation approaches 1% of the general population in Japan. We have begun a collaborative molecular epidemiology study to examine the cancer risk in carriers of mutations in XP DNA repair genes. Chemoprevention of skin cancer in XP with oral 13-cis retinoic acid was found to be effective in preventing skin cancers but very toxic. The lowest effective dose varied in different patients.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Intramural Research (Z01)
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National Cancer Institute Division of Basic Sciences
United States
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Emmert, Steffen; Kraemer, Kenneth H (2013) Do not underestimate nucleotide excision repair: it predicts not only melanoma risk but also survival outcome. J Invest Dermatol 133:1713-7
Wang, Yun; Digiovanna, John J; Stern, Jere B et al. (2009) Evidence of ultraviolet type mutations in xeroderma pigmentosum melanomas. Proc Natl Acad Sci U S A 106:6279-84
Oh, Kyu-Seon; Imoto, Kyoko; Boyle, Jennifer et al. (2007) Influence of XPB helicase on recruitment and redistribution of nucleotide excision repair proteins at sites of UV-induced DNA damage. DNA Repair (Amst) 6:1359-70
Kraemer, Kenneth H; Sander, Miriam; Bohr, Vilhelm A (2007) New areas of focus at workshop on human diseases involving DNA repair deficiency and premature aging. Mech Ageing Dev 128:229-35
Kraemer, K H; Patronas, N J; Schiffmann, R et al. (2007) Xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome: a complex genotype-phenotype relationship. Neuroscience 145:1388-96
Emmert, Steffen; Wetzig, Tino; Imoto, Kyoko et al. (2006) A novel complex insertion/deletion mutation in the XPC DNA repair gene leads to skin cancer in an Iraqi family. J Invest Dermatol 126:2542-4
Khan, Sikandar G; Oh, Kyu-Seon; Shahlavi, Tala et al. (2006) Reduced XPC DNA repair gene mRNA levels in clinically normal parents of xeroderma pigmentosum patients. Carcinogenesis 27:84-94
Hirai, Yuko; Kodama, Yoshiaki; Moriwaki, Shin-Ichi et al. (2006) Heterozygous individuals bearing a founder mutation in the XPA DNA repair gene comprise nearly 1% of the Japanese population. Mutat Res 601:171-8
Liang, Christine; Morris, Andrea; Schlucker, Sebastian et al. (2006) Structural and molecular hair abnormalities in trichothiodystrophy. J Invest Dermatol 126:2210-6
Schlucker, S; Liang, C; Strehle, K R et al. (2006) Conformational differences in protein disulfide linkages between normal hair and hair from subjects with trichothiodystrophy: a quantitative analysis by Raman microspectroscopy. Biopolymers 82:615-22

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