Published online Sep 15, 2003. doi: 10.3748/wjg.v9.i9.1925
Revised: April 3, 2003
Accepted: April 11, 2003
Published online: September 15, 2003
AIM: To explore the instabilities, polymorphisms and other variations of mitochondrial D-loop region and downstream gene 12S rRNA-tRNAphe in gastric cancers, and to study their relationship with gastric cancer.
METHODS: Three adjacent regions (D-loop, tRNAphe and 12S rRNA) were detected for instabilities, polymorphisms and other variations via PCR amplification followed by direct DNA sequencing in 22 matched gastric cancerous tissues and para-cancerous normal tissues.
RESULTS: PolyC or (CA)n instabilities were detected in 13/22(59.1%) gastric cancers and 9/22(40.9%) in the control (P > 0.05). There existed 2/12(16.7%) and 6/10(60%) alterations of 12S rRNA-tRNAphe in well differentiated gastric cancers and poorly differentiated ones, respectively (P < 0.05). Some new variations were found, among which np 318 and np 321 C-T transitions in D-loop region were two of the five bases for H-strand replication primer. np 523 AC-deletion and np 527 C-T transition occurred at mtTF1 binding site (mtTFBS), which were associated with the transcription of downstream mitochondrial genome. Seven samples showed the np 16182 polyC instabilities, five of which simultaneously showed np 16189 T-C transitions.
CONCLUSION: There is no statistic significance of instabilities and polymorphisms in mitochondrial D-loop region between gastric cancerous and para-cancerous normal tissues, which suggests that the instability might relate to heredity or be dependent on aging. There is a significant correlation between differentiation degree of gastric cancer and variant frequencies of 12S rRNA-tRNAphe. The poorly differentiated gastric cancers are more prone to 12S rRNA-tRNAphe variations, or gastric cancers with 12S rRNA-tRNAphe variations are more likely to be poorly differentiated. np 16189 T-C transition may be one of the important reasons for polyC instability in gastric cancer.