DETECTION OF SOMATIC MUTATIONS IN THE MITOCHONDRIAL-DNA CONTROL REGION OF COLORECTAL AND GASTRIC TUMORS BY HETERODUPLEX AND SINGLE-STRAND CONFORMATION ANALYSIS

Each entire hypervariable region of the mitochondrial DNA control regi on was screened for mutations from paired normal and tumor DNA corresp onding to a group of 21 patients (13 colorectal and 8 gastric adenocar cinomas) using both heteroduplex analysis and single-strand conformati on analysis. These two mutation scanning strategies allowed the identi fication of sequence alterations in 3/13 (23%) colorectal tumors and i n 3/8 (37%) gastric tumors; Heteroduplex analysis showed the heteropla smic state of the majority of these tumor mutations. Sequence analysis revealed two A:T/G:C transitions (nucleotide positions: 16241 and 161 66) in hypervariable region 1 (HV1) and two C:GIT:A transitions (nucle otide positions: 76 and 312), one A:T/G:C transition (nucleotide posit ion: 93), a 1-basepair C:G deletion (nucleatide position: 309), and a 2-base-pair CC:GG insertion (nucleotide position: 309) in the HV 2 reg ion. A considerable proportion of these mutations was found in homopol ymeric regions which are highly polymorphic among humans. Different me chanisms (clonal expansion, increased oxidative damage, and nuclear mu tator mutations) were suggested to explain the increased mitochondrial DNA mutation rate observed in cancer.