Repository logo

Multilocus Inherited Neoplasia Allele Syndrome (MINAS): an update.

Published version

Change log


Andreou, Avgi 
Hearn, Timothy 
Genomics England Research Consortium 


Multi-locus Inherited Neoplasia Allele Syndrome (MINAS) refers to individuals with germline pathogenic variants in two or more cancer susceptibility genes(CSGs). With increased use of exome/genome sequencing it would be predicted that detection of MINAS would become more frequent. Here we review recent progress in knowledge of MINAS. A systematic literature search for reports of individuals with germline pathogenic variants in 2 or more of 94 CSGs was performed. In addition, participants with multiple primary tumours who underwent genome sequencing as part of the Rare Disease arm of the UK 100,000 Genomes Project were interrogated to detect additional cases. We identified 385 MINAS cases (211 reported in the last 5 years, 6 from 100,000 genomes participants). Most (287/385) cases contained at least one pathogenic variant in either BRCA1 or BRCA2. 108/385 MINAS cases had multiple primary tumours at presentation and a subset of cases presented unusual multiple tumour phenotypes. We conclude that, as predicted, increasing numbers of individuals with MINAS are being have been reported but, except for individuals with BRCA1/BRCA2 MINAS, individual CSG combinations are generally rare. In many cases it appears that the clinical phenotype is that which would be expected from the effects of the constituent CSG variants acting independently. However, in some instances the presence of unusual tumour phenotypes and/or multiple primary tumours suggests that there may be complex interactions between the relevant MINAS CSGs. Systematic reporting of MINAS cases in a MINAS database (e.g. ) will facilitate more accurate prognostic predictions for specific CSG combinations.


Funder: Cancer Research UK (CRUK); doi:


Alleles, Exome, Genetic Predisposition to Disease, Germ-Line Mutation, Humans, Neoplasms, Multiple Primary, Exome Sequencing

Journal Title

Eur J Hum Genet

Conference Name

Journal ISSN


Volume Title



Springer Science and Business Media LLC
National Institute for Health and Care Research (IS-BRC-1215-20014)
Medical Research Council (MC_PC_14089)