Mitochondrial DNA deletions in skin from melanoma patients.
We measured the cellular levels of two types of mitochondrial DNA (mtDNA) deletions--the 4977-bp common deletion and recently identified UVB-induced deletion of 5128 bp--in apparently normal skin obtained from wide excisions in melanoma patients. The number of deleted mtDNAs as well as the total mtDNA copy number was highly variable, but the number of deletions increased with age of the donor almost 12-fold across the age range of the patients. Patients were scored for degree of overall pigmentation and response to sunlight by a phenotypic index (PI). The relative levels of both types of mtDNA deletions were much more abundant in the intermediate PI groups compared with either the low or high PI groups. In the intermediate PI group, melanomas were also seen later in life. Unexpectedly, the complement of total mitochondrial genomes was more than twofold higher in the low PI group than in the other PI groups. This may reflect a proliferative response to DNA damage induced by solar radiation in the high-risk group.
Hubbard
Karen
K
Department of Biology, The City College of New York, Convent Ave and 160th St, New York, NY 10031, USA.
Steinberg
Mark L
ML
Hill
Helene
H
Orlow
Irene
I
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D016014:Linear Models; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D011795:Surveys and Questionnaires
D004272:DNA, Mitochondrial