title: High frequency of mitochondrial genome instability in human endometrial carcinomas.
abstract: To investigate the occurrence of somatic mitochondrial DNA (mtDNA) mutations in human primary endometrial carcinomas, we sequenced the D-loop region, the 12S and 16S rRNA genes of mtDNA of cancer tissues and their matched normal controls. About 56% (28 out of 50) of cases carry one or more somatic changes in mtDNA including deletion, point mutation and mitochondrial microsatellite instability (mtMSI), namely the change in length of short base-repetitive sequences of mtDNA. In particular, mtMSI was frequently detected in 89% (25 out of 28) of all the cases carrying somatic changes followed by point mutations (25%; seven out of 28) and deletion (3.5%; one out of 28). The CCCCCTCCCC sequences located in the Hypervariable Regions I and II of the D-loop and 12S rRNA gene are instability hot spot regions in endometrial carcinomas. It is suggested that errors in replication may account for the high frequency of mtMSI in human endometrial carcinomas. The relatively high prevalence of mtMSI may be a potential new tool for detection of endometrial cancer.
authors.affiliation: Department of Obstetrics and Gynaecology, Queen Mary Hospital, University of Hong Kong.
authors.forename: V W S
authors.initials: VW
authors.lastname: Liu
authors.forename: H J
authors.initials: HJ
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: P C K
authors.initials: PC
authors.lastname: Tsang
authors.forename: A N Y
authors.initials: AN
authors.lastname: Cheung
authors.forename: P M
authors.initials: PM
authors.lastname: Chiu
authors.forename: T Y
authors.initials: TY
authors.lastname: Ng
authors.forename: L C
authors.initials: LC
authors.lastname: Wong
authors.forename: P
authors.initials: P
authors.lastname: Nagley
authors.forename: H Y S
authors.initials: HY
authors.lastname: Ngan
mesh_terms: D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000097:blood / Q000235:genetics*; D018900:Dinucleotide Repeats; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D015894:Genome, Human; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D018895:Microsatellite Repeats / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012334:RNA, Neoplasm / Q000032:analysis; D012335:RNA, Ribosomal / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D012334:RNA, Neoplasm; D012335:RNA, Ribosomal; D012336:RNA, Ribosomal, 16S; C075526:RNA, ribosomal, 12S