Although Brazilian publications on BRCA mutations predisposing to breast/ovarian cancer have increased in the last five years, the genetic Background of this population is still underrepresented. Mostly, screening has been performed in patients from south-southeast states who met the NCCN guidelines. We present a cohort of breast/ovarian cancer patients, in a private laboratory with a wide market capillarity, where a subset of patients without strict criteria may have access to the test on medical request.
A total of 1,284 consecutive patients were referred for molecular screening to a private laboratory between January 2017-March 2019. Next-generation sequencing and multiplex ligation-dependent probe amplification (MLPA) for BRCA1/2 genes were performed for all patients, except for 15 that were evaluated only by MLPA. Bioinformatic tools with specific algorithms for variant calling and annotation were employed.
Pathogenic germline variants were identified in 12% (n = 156) of patients: 61% in BRCA1 and 39% in BRCA2. To our knowledge, 25 BRCA2 and 17 BRCA1 germline mutations have not been previously described in Brazilian reports. Frameshift and nonsense alterations were the most prevalent types (52% and 22%, respectively). While sixty non-recurring mutations were identified, 31 in BRCA1 and 29 in BRCA2, eleven pathogenic variants were detected 3 or more times, 7 BRCA1 and 4 BRCA2. In agreement with previous reports, c.5266dupC, c.3331_3334delCAAG (BRCA1) and c.2808_2811delACAA (BRCA2) were the most frequent variants. One large rearrangement (deletion of exons 15-16) and the Portuguese founder Alu insertion, c.156_157insAlu, both in BRCA2, were also detected. Additionally, three BRCA1 (c.5074 + 1delG; c.131_132delGC; c. 4414delC) and five BRCA2 (c.6407T>G, c.3659dupA, c.3601_3602delinsT, c.8682delA; c.4329delT) novel mutations were observed.
Our results confirm the reported molecular heterogeneity of Brazilian patients, highlighting the identification of 8 germline pathogenic variants not yet described in BRCA 1/2 reference databases. The detected mutations were associated to a vast array of ethnicities, confirming the admixture of Brazilian population.
The authors.
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All authors have declared no conflicts of interest.