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Detection of somatic mutations in the mitochondrial DNA control region of colorectal and gastric tumors by heteroduplex and single‐strand conformation analysis
Author(s) -
Alonso Antonio,
Martin Pablo,
Albarran Cristina,
Aguilera Beatriz,
Garcia Oscar,
Guzman Ana,
Oliva Horacio,
Sancho Manuel
Publication year - 1997
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.1150180504
Subject(s) - heteroduplex , hypervariable region , heteroplasmy , mitochondrial dna , transition (genetics) , point mutation , microbiology and biotechnology , biology , mtdna control region , d loop , mutation , genetics , nucleotide , dna , gene , haplotype , genotype
Each entire hypervariable region of the mitochondrial DNA control region was screened for mutations from paired normal and tumor DNA corresponding to a group of 21 patients (13 colorectal and 8 gastric adenocarcinomas) using both heteroduplex analysis and single‐strand conformation analysis. These two mutation scanning strategies allowed the identification of sequence alterations in 3/13 (23%) colorectal tumors and in 3/8 (37%) gastric tumors. Heteroduplex analysis showed the heteroplasmic state of the majority of these tumor mutations. Sequence analysis revealed two A:T/G:C transitions (nucleotide positions: 16241 and 16166) in hypervariable region 1 (HV1) and two C:G/T:A transitions (nucleotide positions: 76 and 312), one A:T/G:C transition (nucleotide position: 93), a 1‐basepair C:G deletion (nucleotide position: 309), and a 2‐base‐pair CC:GG insertion (nucleotide position: 309) in the HV 2 region. A considerable proportion of these mutations was found in homopolymeric regions which are highly polymorphic among humans. Different mechanisms (clonal expansion, increased oxidative damage, and nuclear mutator mutations) were suggested to explain the increased mitochondrial DNA mutation rate observed in cancer.