ABSTRACT
In families with features of an autosomal-dominant inherited predisposition to early-onset
breast cancer, full sequencing of the coding regions of BRCA1 and BRCA2 will only identify deleterious mutations in just over half of these families (Fig. 1) (1). Inherited
mutations in other tumor suppressor genes, such as p53 and PTEN, will account for less than 1% to 2% of the remaining families. There are several possible explanations for why
these apparent hereditary breast cancer families do not demonstrate a deleterious BRCA1 or BRCA2 mutation including (i) the cluster of cancers is a chance event; (ii) the individual tested may be a phenocopy (i.e., an individual with a sporadic cancer unrelated
to an inherited predisposition that exists within a family); (iii) the inherited predisposition is secondary to a mutation in an as yet unidentified cancer predisposition gene; or (iv) full sequencing of the coding region of BRCA1 and BRCA2 is unable to detect a deleterious mutation that is present in one of the genes.
