Abstract 4295
Background
Founder BRCA1/2 cancer predisposing mutations have been reported in Italian population. We reported the founder BRCA1 mutation, c.4117G>T - p.Glu1373*, recurring in unrelated families of Abruzzo and Lazio regions of Central Italy.
Methods
Preliminary analysis of 17 unrelated families carrying BRCA1 c.4117G>T nonsense mutation reported in the Hereditary Breast/Ovarian Cancer Registry of the Oncology Territorial Care Unit, University of L’Aquila and Genetic Unit, Catholic University of Rome was performed by genetic counselling and peripheral blood collection after written informed consent from affected and unaffected probands. BRCA1/2 genetic analysis were performed by direct sequencing; haplotype analysis was carried out using microsatellite markers in the 17q21 region: D17S846, D17S1328, D17S855 (intragenic), D17S902, D17S806. Post-test genetic counselling was performed to address Therapeutic and/or Preventive Clinical strategies. Geographic area of origin, cancer family trees, cancers affecting the probands were collected. To date, overall 23 unrelated families were enrolled.
Results
In the preliminary analysis, BRCA1 c.4117G>T mutation was identified in 17 unrelated families with familial origin in a territory of Central Italy including Abruzzo and Lazio regions: this mutation was always and significantly associated with the Allelic Variant (AV) BRCA1, c.3119G>A (p.Ser1040Asn), in 52 tested carriers, 20 affected and 32 unaffected. Microsatellite markers confirmed a common haplotype shared by the 52 probands, comprising the region between D17S1328 and D17S902 markers. In overall 23 unrelated families, the association of BRCA1 founder mutation and the AV were identified in 66 tested carriers, 28 affected and 38 unaffected.
Conclusions
The BRCA1 c.4117G>T is a founder mutation prevalent in the territory of Central Italy in Abruzzo and southern Lazio regions, cosegregating with AV BRCA1 c.3119G>A, providing faster identification of affected and unaffected carriers to specifically address therapeutic and preventive clinical pathways for breast, ovarian and BRCA1-related cancers.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Enrico Ricevuto.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1885 - Factors associated with disease progression in patients treated with trametinib in combination with dabrafenib for unresectable advanced BRAFV600-mutant melanoma: an open label, non randomized study
Presenter: Philippe Saiag
Session: Poster Display session 3
Resources:
Abstract
5259 - Integrative RNAseq and Target panel sequencing reveals common and distinct innate and adaptive resistance mechanisms to BRAF inhibitors
Presenter: Phil Cheng
Session: Poster Display session 3
Resources:
Abstract
5619 - Effective treatment with T-VEC monotherapy in Stage IIIB/C-IVM1a Melanoma of the Head & Neck Region
Presenter: Viola Franke
Session: Poster Display session 3
Resources:
Abstract
5666 - Re-introduction of T-VEC Monotherapy in Recurrent Stage IIIB/C-IVM1a melanoma is effective
Presenter: Viola Franke
Session: Poster Display session 3
Resources:
Abstract
4117 - Efficacy of talimogene laherparepvec (T-VEC) in melanoma patients (pts) with locoregional (LR) recurrence, including in-transit metastases (ITM): subgroup analysis of the phase 3 OPTiM study
Presenter: Mark Middleton
Session: Poster Display session 3
Resources:
Abstract
5303 - Real Life Use of Talimogene Laherparepvec in Melanoma in Centers in Austria and Switzeland
Presenter: Christoph Hoeller
Session: Poster Display session 3
Resources:
Abstract
4130 - Outcomes of advanced melanoma patients who discontinued pembrolizumab (pembro) after complete response (CR) in the French early access program (EAP)
Presenter: Philippe Saiag
Session: Poster Display session 3
Resources:
Abstract
2050 - Outcome of patients with elevated LDH treated with first-line targeted therapy (TT) or PD-1 based immune checkpoint inhibitors (ICI)
Presenter: Sarah Knispel
Session: Poster Display session 3
Resources:
Abstract
1618 - Comparative-Effectiveness of Pembrolizumab vs. Nivolumab for Patients with Metastatic Melanoma
Presenter: Justin Moser
Session: Poster Display session 3
Resources:
Abstract
3556 - Long-term efficacy of combination nivolumab and ipilimumab for first-line treatment of advanced melanoma: a network meta-analysis
Presenter: Peter Mohr
Session: Poster Display session 3
Resources:
Abstract