A clinical and genetic analysis of multiple primary cancer referrals to genetics services

James Whitworth, Jon Hoffman, Cyril Chapman, Kai Ren Ong, Fiona Lalloo, D. Gareth Evans, Eamonn R. Maher*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Multiple primary malignant tumours (MPMT) are frequently taken as an indicator of potential inherited cancer susceptibility and occur at appreciable frequency both among unselected cancer patients and, particularly, among referrals to cancer genetics services. However, there is a paucity of information on the clinical genetic evaluation of cohorts of MPMT patients representing a variety of tumour types. We ascertained a referral-based series of MPMT cases and describe the patterns of tumours observed. Service-based molecular genetic testing had demonstrated a pathogenic germline variant in an inherited cancer gene in fewer than one in four unselected referrals. To assess for evidence of thus far unidentified variants in those who tested negative, comparisons were made with those who tested positive. This revealed considerable overlap between the two groups with respect to clinical characteristics indicative of an inherited cancer syndrome. We therefore proceeded to test a subset of unexplained MPMT cases (n=62) for pathogenic germline variants in TP53 and PTEN but none were detected. Individuals with MPMT may receive negative genetic test results for a number of reasons, which are discussed. Many of these may be addressed by the increasing application of next generation sequencing techniques such as inherited cancer gene panels.

Original languageEnglish
Pages (from-to)581-587
Number of pages7
JournalEuropean Journal of Human Genetics
Issue number5
Early online date24 Sept 2014
Publication statusPublished - 21 May 2015


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