Multilocus Inherited Neoplasia Alleles Syndrome (MINAS): Case Series and Literature Review

Abstract

Mendelian causes of inherited cancer susceptibility are mostly rare and characterized by variable expression and incomplete penetrance. Phenotypic variability may result from a range of causes including locus heterogeneity, allelic heterogeneity, genetic and environmental modifier effects or chance. Another potential cause is the presence of two or more inherited cancer predisposition alleles in the same individual. Though the frequency of such occurrences might be predicted to be low, such cases have probably been under ascertained because standard clinical practice has been to test candidate inherited cancer genes sequentially until a pathogenic mutation is detected. However, recent advances in next generation sequencing technologies now provide the opportunity to perform simultaneous parallel testing of large numbers of inherited cancer genes. Here we provide examples of patients who harbor pathogenic mutations in multiple inherited cancer genes and review previously published examples to illustrate the complex genotype-phenotype relationships in these cases. We suggest that clinicians should proactively consider the likelihood of this phenomenon (referred to here as Multilocus Inherited Neoplasia Alleles Syndrome (MINAS)) in patients with unusual inherited cancer syndrome phenotypes. To facilitate the clinical management of novel cases of MINAS we have established a database to collect information on what is likely to be an increasingly recognized cohort of such individuals.