Detection and analysis of cancer genes amplified from bone material of a Scythian royal burial in Arzhan near Tuva, Siberia.
Molecular paleopathology has become an emerging field that helps to characterize molecular markers of past disease. Especially highly sensitive genetic techniques such as PCR are an important means of unraveling changes in ancient DNA extracted from bone tissue, teeth and mummified soft tissue. In the present study, excavated bone material from the skeleton of a Scythian sovereign, morphologically and immunohistochemically suspicious of a metastatic prostate carcinoma, was analyzed by PCR for amplifiable human gene sequences. Short sequences of the human GADD153 DNA repair gene and p53 tumor suppressor gene were detectable which revealed the absence of mutations according to the data of automatic sequencing. Using bisulfite-treated DNA from the bone, methylation-specific PCR detected hypermethylated promoter sequences of the p14ARF tumor suppressor gene. In summary, these data show that it is possible: a) to amply short human DNA stretches from 2,500-year-old bone material, b) to detect tumorigenetically important genes within this DNA, c) to detect epigenetically modified DNA in ancient bone material. The finding of hypermethylated p14ARF sequences merits attention because this may indicate an intraosseal neoplastic process and may corroborate the hypothesis of prostate cancer.
Schlott
Thilo
T
Department of Pathology, Georg August Universitaet, Goettingen, Germany. thiloschlott@web.de
Eiffert
Helmut
H
Schmidt-Schultz
Tyede
T
Gebhardt
Melanie
M
Parzinger
Hermann
H
Schultz
Michael
M
D000885:Anthropology, Physical / Q000379:methods; D001842:Bone and Bones / Q000737:chemistry*; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics*; D005784:Gene Amplification; D016158:Genes, p53; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D012800:Siberia; D051742:Transcription Factor CHOP / Q000235:genetics*; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*
C497249:DDIT3 protein, human; D004273:DNA, Neoplasm; D025803:Tumor Suppressor Protein p14ARF; D051742:Transcription Factor CHOP