IMPORTANCE: Genetic testing of hereditary cancer using comprehensive gene panels 
can identify patients with more than one pathogenic mutation in high and/or 
moderate-risk-associated cancer genes. This phenomenon is known as multilocus 
inherited neoplasia alleles syndrome (MINAS), which has been potentially linked 
to more severe clinical manifestations.
OBJECTIVE: To determine the prevalence and clinical features of MINAS in a large 
cohort of adult patients with hereditary cancer homogeneously tested with the 
same gene panel.
PATIENTS AND METHODS: A cohort of 1023 unrelated patients with suspicion of 
hereditary cancer was screened using a validated panel including up to 135 genes 
associated with hereditary cancer and phakomatoses.
RESULTS: Thirteen (1.37%) patients harbouring two pathogenic mutations in 
dominant cancer-predisposing genes were identified, representing 5.7% (13/226) 
of patients with pathogenic mutations. Most (10/13) of these cases presented 
clinical manifestations associated with only one of the mutations identified. 
One case showed mutations in MEN1 and MLH1 and developed tumours associated with 
both cancer syndromes. Interestingly, three of the double mutants had a young 
age of onset or severe breast cancer phenotype and carried mutations in moderate 
to low-risk DNA damage repair-associated genes; two of them presented biallelic 
inactivation of CHEK2. We included these two patients for the sake of their 
clinical interest although we are aware that they do not exactly fulfil the 
definition of MINAS since both mutations are in the same gene.
CONCLUSIONS AND RELEVANCE: Genetic analysis of a broad cancer gene panel 
identified the largest series of patients with MINAS described in a single 
study. Overall, our data do not support the existence of more severe 
manifestations in double mutants at the time of diagnosis although they do 
confirm previous evidence of severe phenotype in biallelic CHEK2 and other DNA 
repair cancer-predisposing genes.