Breast cancer risk in neurofibromatosis type 1 is a function of the type of <i>NF1</i> gene mutation: a new genotype-phenotype correlation

Abstract

These data strongly support the hypothesis that certain constitutional mutation types, and indeed certain specific variants in <i>NF1</i> confer different risks of BC. The lack of large deletions and excess of nonsenses and missenses is consistent with gain of function mutations conferring risk of BC, and also that neurofibromin may function as a dimer. The observation that somatic <i>NF1</i> amplification can occur independently of <i>ERBB2</i> amplification in sporadic BC supports this concept. A prospective clinical-molecular study of NF1-BC needs to be established to confirm and build on these findings, but regardless of <i>NF1</i> mutation status patients with NF1-BC warrant testing of other BC-predisposing genes.