Lack of mutation at p16INK4A gene but expression of aberrant p16INK4A RNA transcripts in human ovarian carcinoma.
Alterations of the p16INK4A gene are frequent in various human cancers. We investigated p16INK4A gene status in 20 ovarian carcinomas by PCR (polymerase chain reaction), PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) and sequencing techniques. None of the primary tumors showed any mutational or deletional events. However, 19 out of 20 tumors displayed both a methylated and an unmethylated p16INK4A promoter. In some of these samples, we detected aberrant p16INK4A transcripts, with partial deletions of both exons 1 and 2, which could not encode a functional p16INK4A protein. The sequences of the aberrant mRNA revealed common 4-7 nucleotide sequences before and after the deleted region, which might cause abnormal splicing of mRNA transcripts. These results suggest that both promoter methylation and aberrant mRNA processing may interfere with p16INK4A expression in ovarian tumors.
Suh
S I
SI
Department of Microbiology and Institute for Medical Science, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu, South Korea. seong@dsmc.or.kr
Cho
J W
JW
Baek
W K
WK
Suh
M H
MH
Carson
D A
DA
D001483:Base Sequence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm; D012689:Sequence Homology, Nucleic Acid
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm