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open access
Abstract (provisional)
Background
High-grade serous ovarian cancers are a distinct histological subtype of ovarian cancer
often characterised by a dysfunctional BRCA/Fanconi anaemia (search) (BRCA/FA) pathway, which
is critical to the homologous recombination DNA repair machinery. An impaired BRCA/FA
pathway sensitises tumours to the treatment with DNA cross-linking agents and to PARP
inhibitors. The vast majority of inactivating mutations in the BRCA/FA pathway are
in the BRCA1 and BRCA2 genes and occur predominantly in high-grade serous cancer.
Another member of the BRCA/FA pathway, PALB2 (FANCN), was reported to have been inactivated
by DNA methylation in some sporadic ovarian cancers. We therefore sought to investigate
the role of PALB2 methylation in high-grade serous ovarian cancers.
Finding: PALB2 methylation was investigated in 92 high-grade serous ovarian cancer
samples using methylation-sensitive high-resolution melting analysis. DNA methylation
of PALB2 was not detected in any of the ovarian cancer samples investigated.
Conclusion
Epigenetic silencing by DNA methylation of PALB2 is not a common event in high-grade
serous ovarian cancers.
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