Somatic D-loop mitochondrial DNA mutations are frequent in uterine serous carcinoma.
The mitochondria plays a role in apoptosis. Its genome is also more susceptible to mutations because of high levels of reactive oxygen species and limited repair mechanisms. The D-loop of mitochondrial DNA (mtDNA) contains essential transcription and replication elements, and mutations in this region might alter the rate of DNA replication. We examined genetic alterations in the D-loop region of mtDNA in uterine serous carcinoma (USC) samples and their paired normal adjacent endometrium. DNA was extracted after laser-capture microdissection of paraffin-embedded tissues from eight patients with USC. The entire D-loop genome was amplified using nine pairs of overlapping primers. Denatured polymerase chain reaction (PCR) products were subjected to single-strand conformation polymorphism (SSCP) analysis. Somatic mtDNA alterations were detected in five tumours (63%). Our study indicates that mtDNA D-loop sequence alterations occur at a high frequency in USC suggesting that mtDNA mutations may play a role in the development of USC.
Pejovic
Tanja
T
Division of Gynecologic Oncology, Yale University School of Medicine, New Haven, CT, USA.
Ladner
Daniela
D
Intengan
Marilyn
M
Zheng
Karl
K
Fairchild
Tracy
T
Dillon
Deborah
D
Easley
Samantha
S
Dillon
Dionne
D
Marchetti
David
D
Schwartz
Peter
P
Lele
Shashikant
S
Costa
Jose
J
Odunsi
Kunle
K
D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D014594:Uterine Neoplasms / Q000235:genetics*
D004272:DNA, Mitochondrial