Abstract 1687
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3082 - Prognostic and predictive role of body mass index (BMI) in metastatic colorectal cancer (mCRC): a pooled analisys of TRIBE and TRIBE-2 studies by GONO
Presenter: Emanuela Dell'Aquila
Session: Poster Display session 2
Resources:
Abstract
3618 - Drug holidays and overall survival in patients treated for metastatic colorectal cancer
Presenter: Silvio Ken Garattini
Session: Poster Display session 2
Resources:
Abstract
6111 - Quality of life during 1st-line FOLFOXIRI+/- panitumumab in RAS wild-type metastatic colorectal cancer: Results from the randomized VOLFI trial (AIO KRK-0109)
Presenter: Michael Geissler
Session: Poster Display session 2
Resources:
Abstract
1042 - A biomarker combination indicating resistance to FOLFOX plus bevacizumab in metastastic colorectal cancer : results of phase I of the PERMAD trial
Presenter: Thomas Seufferlein
Session: Poster Display session 2
Resources:
Abstract
3291 - Microsatellite Instability (MSI) status and prognosis in colorectal cancer: meta-analysis
Presenter: James Toh
Session: Poster Display session 2
Resources:
Abstract
2046 - Choosing the right strategy based on individualized treatment effect predictions: Combination versus sequential chemotherapy in patients with metastatic colorectal cancer.
Presenter: Miriam Koopman
Session: Poster Display session 2
Resources:
Abstract
2589 - Noninferiority on overall survival of every-2-weeks vs weekly schedule of cetuximab for first-line treatment of RAS wild-type metastatic colorectal cancer
Presenter: Stefan Kasper
Session: Poster Display session 2
Resources:
Abstract
4944 - POLAF study: Efficacy and safety of FOLFIRI/aflibercept in a phase II trial in patients with metastatic colorectal cancer: Results of plasmatic prognostic and predictive markers
Presenter: Maria Elena Elez Fernandez
Session: Poster Display session 2
Resources:
Abstract
2042 - The accuracy of the clinical PCI score in patients with peritoneal carcinomatosis of colorectal cancer
Presenter: Nadine De Boer
Session: Poster Display session 2
Resources:
Abstract
2667 - The impact of late-line treatment on overall survival (OS) from the initiation of first-line chemotherapy (CT) for patients (pts) with metastatic colorectal cancer (mCRC).
Presenter: Takeshi Kawakami
Session: Poster Display session 2
Resources:
Abstract