UNEXPECTED RESULTS FROM MULTIGENE PANELS IN HEREDITARY CANCER SYNDROME AT A LATIN-AMERICAN CANCER CENTER

Introduction: Approximately 10% of cancers can be attributed to a germline mutation, confirming an inherited cancer syndrome. Hereditary Cancer Syndrome (HCS) has significant implications in early screening and prevention for the proband and at-risk family members and also is critical for modern oncologic care. Multigene panels have been increasingly used by experts and shown to be a cost-effective approach to diagnose HCS in genetic counseling practice, with the advent of Next-Generation Sequencing (NGS). One relevant role of multigene panels versus syndrome-specific germline testing is for patients with clinical histories spanning several possible diagnoses and for patients with suspicious clinical histories not meeting diagnostic criteria for a specific HCS. However, more multigene panels are performed, more incidental findings are revealed in genes whose clinical implications are not fully understood. Purpose: our aim was estimate the rate of unexpected results in multigene test for HCS in patients followed in Oncogenetics Department at A.C. Camargo Cancer Center (ACCCC) Patients and Methods: Retrospective cross-sectional study. Data from patients seen at the Oncogenetics Department of ACCCC who carried out multigene panels to investigate hereditary cancer syndrome, from January 2014 to July 2018. Unexpected result was defined when the affected gene was not considered for the initial diagnostic criteria. Results: A total of 535 patients performed multigene panels based on genetic counseling, 492 females and 44 males with an average age of 48 years. Panels of 5-79 genes were performed in fifteen different laboratories. Of these, in 136 (25.4%) were found a pathogenic variant, and in 187 (34.9%) was found at least one variant of uncertain significance (VUS). Among the positive results, 15.4% (21 out of 136) were considered as unexpected Results: TP53 (6), monoallelic MUTYH (5), NBN (1), BRIP (1), BARD1(1), DIS3L2 (1), SPINK1 (1), MLH3 (1), MSH6 (1), NF1 (1), CHEK2 (1) and SBDS (1) genes. Conclusions: our data point to a moderate-to-high rate of unexpected results in multigene panels for HCS and reinforce the challenge of careful interpretation these unexpected findings in the Genetic Counseling, including actionable genes and genes that can not change the medical management.

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Artikel online veröffentlicht:
23. Oktober 2019