RT Journal Article SR Electronic T1 Assessment of mismatch repair deficiency in ovarian cancer JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 687 OP 691 DO 10.1136/jmedgenet-2020-107270 VO 58 IS 10 A1 Emma J Crosbie A1 Neil A J Ryan A1 Rhona J McVey A1 Fiona Lalloo A1 Naomi Bowers A1 Kate Green A1 Emma R Woodward A1 Tara Clancy A1 James Bolton A1 Andrew J Wallace A1 Raymond F McMahon A1 D Gareth Evans YR 2021 UL http://jmg.bmj.com/content/58/10/687.abstract AB Background Hereditary causes of ovarian cancer include Lynch syndrome, which is due to inherited pathogenic variants affecting one of the four mismatch repair genes involved in DNA repair. The aim of this study was to evaluate tumour mismatch repair deficiency and prevalence of Lynch syndrome in high-risk women referred to the Manchester Centre for Genomic Medicine with ovarian cancer over the past 20 years.Methods Women with ovarian cancer diagnosed before the age of 35 years and/or with a suggestive personal or family history of Lynch syndrome cancers underwent tumour testing with immunohistochemistry for mismatch repair deficiency and, where indicated, MLH1 promoter methylation testing followed by constitutional testing for Lynch syndrome.Results In total, 261 ovarian cancers were tested and 27 (10.3%; 95% CI 6.9% to 14.7%) showed mismatch repair deficiency by immunohistochemistry. Three of 7 with MLH1 loss showed MLH1 promoter hypermethylation, and 18 of the remaining 24 underwent constitutional testing for Lynch syndrome. A further 15 women with mismatch repair proficient tumours underwent constitutional testing because of a strong family history of Lynch syndrome cancers. Pathogenic variants were identified in 9/33 (27%) women who underwent constitutional testing, aged 33–59 years (median 48 years), including one whose tumour was mismatch repair proficient. Most Lynch syndrome tumours were of endometrioid histological subtype.Conclusions Tumour mismatch repair deficiency identified by immunohistochemistry is a useful prescreen for constitutional testing in women with ovarian cancer with personal or family histories suggestive of Lynch syndrome.Data are available from the corresponding author on reasonable request.