No evidence for PALB2 methylation in high-grade serous ovarian cancer

Kathryn Alsop,Thomas Mikeska,David Dl Bowtell,Gillian Mitchell,Alexander Dobrovic

doi:10.1186/1757-2215-6-26

Kathryn Alsop, Thomas Mikeska + Show 3 more

Open Access

https://doi.org/10.1186/1757-2215-6-26

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Abstract

BackgroundHigh-grade serous ovarian cancers are a distinct histological subtype of ovarian cancer often characterised by a dysfunctional BRCA/Fanconi anaemia (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.FindingPALB2 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.ConclusionEpigenetic silencing by DNA methylation of PALB2 is not a common event in high-grade serous ovarian cancers.

Highlights

High-grade serous ovarian cancers are a distinct histological subtype of ovarian cancer often characterised by a dysfunctional BRCA/Fanconi anaemia (BRCA/FA) pathway, which is critical to the homologous recombination DNA repair machinery
The largest group are high-grade serous ovarian cancers, of which a substantial proportion are characterised by an impaired BRCA/Fanconi anaemia (BRCA/FA) pathway [2,3]
The BRCA/FA pathway is a key part of the homologous recombination DNA repair machinery and includes the BRCA1 and BRCA2 genes as well as members of the Fanconi anaemia complementation group

Summary

Introduction

High-grade serous ovarian cancers are a distinct histological subtype of ovarian cancer often characterised by a dysfunctional BRCA/Fanconi anaemia (BRCA/FA) pathway, which is critical to the homologous recombination DNA repair machinery. Conclusion: Epigenetic silencing by DNA methylation of PALB2 is not a common event in high-grade serous ovarian cancers. The largest group are high-grade serous ovarian cancers, of which a substantial proportion are characterised by an impaired BRCA/Fanconi anaemia (BRCA/FA) pathway [2,3].

Results

Conclusion