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Review
. 2022 Mar;30(3):265-270.
doi: 10.1038/s41431-021-01013-6. Epub 2022 Jan 4.

Multilocus Inherited Neoplasia Allele Syndrome (MINAS): an update

Anthony McGuigan  1 , James Whitworth  2 , Avgi Andreou  2 , Timothy Hearn  2 ; Genomics England Research Consortium; Marc Tischkowitz  2 , Eamonn R Maher  3
Collaborators, Affiliations
Review

Multilocus Inherited Neoplasia Allele Syndrome (MINAS): an update

Anthony McGuigan et al. Eur J Hum Genet. 2022 Mar.

Abstract

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. https://databases.lovd.nl/shared/diseases/04296 ) will facilitate more accurate prognostic predictions for specific CSG combinations.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Cumulative frequency of reported individuals with MINAS cases from 1996 to 2020. (6 participants the from 100,000 genome project were included in the total for 2020 project were included in the total for 2020 figures).
Fig. 2
Fig. 2
Circos plots illustrating combinations of cancer susceptibility genes (CSGs) involved in individual cases of MINAS (n = 385).
See this image and copyright information in PMC

Comment in

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