N21: Detection of a pathogenic variant on Partner and Localiser Breast cancer 2 (PALB2) gene in Lynch Syndrome family

C. M. Watt1, M. Kharbanda1, D. Moore2, R. Davidson1

1 -Clinical Genetics, West of Scotland Genetic Services. 2 – Molecular Genetics, South East of Scotland Genetic Services.

Aim: A 48 year old woman was referred to the West of Scotland Genetic Services with a diagnosis of metastatic breast cancer and was subsequently shown to have a maternal family history of bowel cancer fulfilling the Amsterdam criteria. The pathology of the breast tumour was oestrogen receptor negative, progesterone receptor negative and HER 2 negative. Previously at the age of 44 years the woman had been diagnosed with oestrogen receptor positive and progesterone receptor positive breast cancer.

Method: The patient was offered mutation analysis of the highly penetrant BRCA 1 gene and BRCA 2 gene and panel testing.

Results: Analysis detected a heterozygous pathogenic PALB2 variant c.1592_1593delInsA, p.(Leu531fs). A variant resulting in the same frameshift c.1592ddel, p.(Leu531fs) is a known pathogenic variant that has been shown to result in a truncated unstable protein which is associated a significant risk of breast cancer. No pathogenic variants were detected on BRCA1, BRCA 2, ATM, CHEK 2, MLH1, MSH2, MSH6, MUTYH, PTEN, STK11 and TP53 genes. Inheritance was determined by accessing stored tumour tissue from the time of her mother’s surgery for rectal cancer in 1991. Analysis confirmed the presence of the PALB2 variant.

Conclusion: Predictive testing is now available to the wider family.