Abstract CN4
Background
Approximately 5 to 10% of all cancers are caused by inherited germline mutations, many of which are associated with different Hereditary Cancer Syndromes (HCS). The use of next-generation DNA sequencing (NGS) in clinical practice has deployed a suite of technologies that have drastically increased the quality and decreased the cost of sequencing compared to Sanger sequencing. Moreover, moderate and high penetrance genes have been described in patients with phenotypes that were previously unrelated. Such advances in molecular diagnosis allowed some families with multiple cases of cancer who remained undiagnosed to be retested. In this study, we aim to recontact patients who performed molecular tests with negative/inconclusive results and who might benefit to be re-evaluated from a current molecular diagnostic perspective.
Methods
We performed an active search in the Hereditary Cancer Registry of Hospital Sirio-Libanes, São Paulo, Brazil, for patients who fulfilled clinical criteria for Hereditary Breast and Ovarian Cancer Syndrome, Lynch Syndrome or Li-Fraumeni Syndrome who have tested negative/inconclusive by Sanger sequencing for the related gene or by NGS limited panels (less than 21 genes) or no MLPA or no analysis of large deletions or insertions by CNV. Patients who have agreed to receive an 84 cancer gene panel by NGS have been included.
Results
We have identified in the Hereditary Cancer Registy 327 patients who met clinical criteria for HBOC, 25 for Lynch Syndrome and 52 for Li-Fraumeni Syndrome and did not have a pathogenic germline variant detected. A total of 102 patients agreed to participate. Until now, 34 unrelated patients were tested for an 84 cancer gene panel. Pathogenic variants, previously undetected, were found in 10 (10/34-29.9%), including BLM, RAD51C, PALB2, MUTYH (2), SDHA, TP53(2), BRCA1, DIS3L2 genes.
Conclusions
Patients who received genetic counseling and testing with limited techniques must be re-contacted for a new evaluation, using a current molecular diagnostic perspective. Recontacting these families becomes a challenge in care and prevention and nurses can have an important role in development of strategies that allow the detection and contact of those patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Hospital Sirio-Libanes.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.