Germline BRCA-Lynch syndrome MINAS: report of six Argentinian families and a systematic review of the literature

BRCA1/2

Co-occurrence of germline pathogenic variants in BRCA1/BRCA2 and a mismatch repair gene

The co-occurrence of germline pathogenic or likely pathogenic variants in BRCA1/BRCA2 and a mismatch repair gene defines BRCA-Lynch multi-locus inherited neoplasia allele syndrome (MINAS), a rare overlap of the two most frequent hereditary cancer syndromes. The authors report six Argentinian families and perform a systematic review of the literature (40 publications), for a total of 92 patients from 69 families. The phenotype shows a balanced distribution of BRCA- and Lynch-related tumours, and tumours outside both spectra are uncommon. Carriers of MLH1 and MSH2/EPCAM variants were more likely to have at least two tumours (OR 3.60; 95% CI 1.29-10.55) and extracolonic tumours (OR 3.28; 95% CI 1.26-8.84) than carriers of MSH6 and PMS2 variants, consistent with known Lynch syndrome genotype-phenotype correlations. In these patients ascertained through personal or family history, both syndromes appear to be expressed independently.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Practical message: with no demonstrated synergy, each component is managed according to the recommendations for its own syndrome. Clinical ascertainment and pooling of published cases expose the analysis to selection bias, and the question of a synergistic effect remains open, as the authors acknowledge. Wider use of multigene panels, exome and genome sequencing will make such dual diagnoses more frequent.

Analysis by Dr Thibaut Benquey