Multilocus Inherited Neoplasia Allele Syndrome (MINAS): an update

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.

Publication DOI: https://doi.org/10.1038/s41431-021-01013-6
Divisions: College of Health & Life Sciences > Aston Medical School
Funding Information: This research was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The University of Cambridge has received salary support (ERM) from the NHS in the East of England through the Clinical Academic Reserve. The views expressed are
Additional Information: Copyright © The Author(s), 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
Uncontrolled Keywords: Alleles,Exome,Genetic Predisposition to Disease,Germ-Line Mutation,Humans,Multiple Primary/genetics,Exome Sequencing,Neoplasms
Publication ISSN: 1476-5438
Last Modified: 04 Jul 2024 07:29
Date Deposited: 04 Jan 2024 17:27
Full Text Link:
Related URLs: https://www.nat ... 431-021-01013-6 (Publisher URL)
PURE Output Type: Review article
Published Date: 2022-03
Published Online Date: 2022-01-04
Accepted Date: 2021-11-15
Authors: McGuigan, Anthony
Whitworth, James
Andreou, Avgi
Hearn, Timothy
Tischkowitz, Marc
Maher, Eamonn R.

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