Multicentre audit reviewing reporting and management of patients with incidentally identified structural aberrations involving high actionability cancer susceptibility genes.

A structural aberration (SA) with secondary implications (SASIs) involving a cancer susceptibility gene is identified on chromosome microarray in approximately 0.6% tests performed on index cases. Identifying a SASI involving a high actionability cancer susceptibility gene (HA-CSG) has important genetic counselling and management implications for the individual and families. In 2019, a UK working group published recommendations for laboratories reporting SASIs involving HA-CSG. This study aims to evaluate whether these recommendations are reflected in the current UK practice. Data from a total of 63 cases of SASIs involving HA-CSGs from nine UK genetics centres were included for audit. The results have shown that 92% of microarray reports have the HA-CSG clearly named on the report, with 70% of reports having the anticipated increased risk of cancer stated. 73% of patients were appropriately managed for the associated cancer risk. For SAs where management was not given as per recommended guidelines, the identified variants were all within-gene duplications, which may represent the uncertainty around their potential to disrupt gene function and their association with true increased cancer susceptibility. This study demonstrates the practical implications of identifying a SA involving a HA-CSG and suggests room for improvement in clinical practice in reporting and management.