Genetic analysis of cancer-implicated MicroRNA in ovarian cancer.
OBJECTIVE
There is accumulating evidence that microRNAs may function like classic tumor suppressor genes but little is known about their mechanism of inactivation in cancer cells. We investigated whether somatic mutations are a common mechanism of inactivation of microRNA genes in ovarian cancer.


METHODS
Ten cancer-implicated microRNA genes were analyzed for somatic mutations in 90 ovarian epithelial cancers and matching normal DNA. High-resolution melt analysis and bidirectional sequencing was used to detect sequence variations.


RESULTS
High-resolution melt analysis and direct sequencing did not identify any somatic mutations but did reveal numerous novel and previously reported germ line base substitutions, deletions, and insertions surrounding the mature microRNA sequences. The majority of variants were detected in the same proportion of non-cancer control individuals suggesting that they do not represent ovarian cancer-predisposing alleles.


CONCLUSIONS
The absence of somatic mutations in any of the 10 cancer-implicated microRNAs in our large cohort of ovarian tumors suggests that this may be an uncommon mechanism of inactivation of microRNAs in ovarian cancer.
Bearfoot
Jennifer L
JL
VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Australia.
Choong
David Y H
DY
Gorringe
Kylie L
KL
Campbell
Ian G
IG
D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm; D035683:MicroRNAs