RESUMO
OBJECTIVE: To calculate and discuss the percentage of imbalance for selected cancer predisposition genes in patients referred for routine diagnostic array comparative genomic hybridisation (CGH). DESIGN: Audit of findings from application of array CGH for patients referred for developmental delay, behavioural abnormalities and birth defects in 4805 patients referred to Guy's and St Thomas' NHS Foundation Trust for cytogenetic investigation from South East London, Kent and East Sussex and other genetic centres across the UK. RESULTS: 29 of 4805 (0.6%) patients examined by array CGH had genomic imbalance of <5 Mb involving cancer predisposition genes. Six patients were referred for syndromes involving cancer predisposition genes; none of the other 23 patients with array CGH findings in cancer predisposition genes had any symptoms/family history stated on their referral form suggestive for the respective syndrome. Twelve whole gene deletions, two partial deletions, 12 duplications, two partial duplications, and one mosaic duplication were observed. In 17/29 patients (59%), inheritance could not be established, eight imbalances were de novo, and four inherited. CONCLUSIONS: This new technology raises the possibility of unexpected findings in cancer predisposition genes. Therefore, the possibility of such findings has to be addressed in pre-test and post-test counselling by genetically trained healthcare professionals. As many of these findings have not been described previously, their clinical significance is unknown and patients need long-term follow-up to determine their clinical relevance. This will enable genetic healthcare professionals to advise such people about their cancer risks and appropriate cancer risk management options.