Overview of the Genetic Causes of Hereditary Breast and Ovarian Cancer Syndrome in a Large French Patient Cohort
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. NGS Analysis
2.3. Variant Interpretation
2.4. Additional Analyzes
3. Results
3.1. Multigene Panel Screening
3.2. Novel Mutations
3.3. Recurrent Mutations
3.4. Identification of Double Mutations
3.5. mRNA Transcript Analysis of Patients with P/LP Splice Variants
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene | Transcript | Gene | Transcript |
---|---|---|---|
BRCA1 | NM_007294.3 | CDH1 | NM_004360.4 |
BRCA2 | NM_000059.3 | MLH1 | NM_000249.3 |
PALB2 | NM_024675.3 | MSH2 | NM_000251.2 |
RAD51C | NM_058216.2 | MSH6 | NM_000179.2 |
RAD51D | NM_002878.3 | PMS2 * | NM_000535.6 |
TP53 | NM_000546.5 | EPCAM ** | NM_002354.2 |
PTEN | NM_000314.6 |
Personal and Familial Criteria | Total | Detection Rate of P/LP Variants, n (%) |
---|---|---|
Breast carcinoma ≤ 31 years | 177 | 23 (13%) |
Breast carcinoma ≤ 36 years | 564 | 23 (14%) |
Male breast carcinoma | 91 | 11 (12%) |
Ovary adenocarcinoma | 759 | 112 (15%) |
Bilateral breast carcinoma | 244 | 33 (14%) |
Free of cancer index case with a strong familial history of HBOC | 108 | 9 (8.3%) |
Index case with both breast and ovarian cancer | 74 | 9 (17.6%) |
Patients previously tested negative for BRCA pathogenic variants retested using the panel of 13 HBOC genes | 492 | 25 (5%) |
Genes | cDNA Position | Protein | Frequency | % |
---|---|---|---|---|
BRCA1 | c.5266dup | p.(Gln1756Profs*14) | 15 | 7.4 |
c.3481_3491del | p.(Glu1161Phefs*3) | 10 | 5 | |
c.1115G>A | p.(Trp372*) | 9 | 4 | |
c.4391del | p.(Pro1464Leufs*2) | 5 | 2 | |
c.4327C>T | p.(Arg1443*) | 4 | 2 | |
c.3756_3759delGTCT | p.(Ser1253Argfs*10) | 4 | 2 | |
c.191G>A | p.(Cys64Tyr) | 4 | 2 | |
BRCA2 | c.4889C>G | p.(Ser1630*) | 11 | 5 |
c.3847_3848delGT | p.Val1283Lysfs*2 | 7 | 4 | |
c.9294C>A | p.(Tyr3098*) | 6 | 3 | |
c.1813dupA | p.(Ile605Asnfs*11) | 6 | 3 | |
c.1310_1313delAAGA | p.(Lys437Ilefs*22) | 6 | 3 | |
c.7680dup | p.(Gln2561Serfs*5) | 5 | 3 | |
c.8364G>A | p.Trp2788* | 4 | 2 | |
c.2612C>A | p.(Ser871*) | 4 | 2 | |
c.5909C>A | p.(Ser1970*) | 4 | 2 | |
RAD51C | c.1026+5_1026+7delGTA | p.(Arg322Serfs*22) | 9 | 25 |
c.965+5G>A | p.(Glu303Trpfs*41) | 7 | 19 | |
RAD51D | c.803G>A | p.(Trp268*) | 5 | 40 |
c.170del | p.(Leu57Argfs*10) | 4 | 30 | |
PALB2 | c.2257C>T | p.(Arg753*) | 3 | 7 |
c.1915G>T | p.(Glu639*) | 3 | 7 |
Gene | Diagnosis | Variant | Protein Effect | Class |
---|---|---|---|---|
Patient 1 | ||||
BRCA1 | Uterus cancer at 30 years. Triple-negative breast carcinoma at 33 years | c.5309G>T | p.(Gly1770Val) | 5 |
BRCA2 | c.7234_7235insG | p.(Thr2412Serfs*2) | 5 | |
Patient 2 | ||||
BRCA1 | Breast carcinoma at 36 years, contralateral triple-negative breast carcinoma at 62 years | c.212+3A>G | p.Cys64fs* | 5 |
RAD51C | c.1026+5_1026+7delGTA | p.(Arg322Serfs*22) | 5 | |
Patient 3 | ||||
BRCA2 | Breast carcinoma at 55 years | c.9097dupA | p.(Thr3033fs) | 5 |
RAD51C | c.905-2del | p.(Glu303Trpfs*41) | 5 | |
Patient 4 | ||||
BRCA2 | Ovarian cancer | c.1842dupT | p.(Asn615*) | 5 |
RAD51C | c.773G>A | p.(Arg258His) | 5 | |
Patient 5 | ||||
BRCA2 | Epithelial thyroid cancer at 29 years Breast carcinoma at 37 years | c.3645_3646delGTinsTAAAAAG | p.(Phe1216Lysfs*14) | 5 |
PTEN | c.1003C>T | p.(Arg335*) | 5 |
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Bouras, A.; Guidara, S.; Leone, M.; Buisson, A.; Martin-Denavit, T.; Dussart, S.; Lasset, C.; Giraud, S.; Bonnet-Dupeyron, M.-N.; Kherraf, Z.-E.; et al. Overview of the Genetic Causes of Hereditary Breast and Ovarian Cancer Syndrome in a Large French Patient Cohort. Cancers 2023, 15, 3420. https://doi.org/10.3390/cancers15133420
Bouras A, Guidara S, Leone M, Buisson A, Martin-Denavit T, Dussart S, Lasset C, Giraud S, Bonnet-Dupeyron M-N, Kherraf Z-E, et al. Overview of the Genetic Causes of Hereditary Breast and Ovarian Cancer Syndrome in a Large French Patient Cohort. Cancers. 2023; 15(13):3420. https://doi.org/10.3390/cancers15133420
Chicago/Turabian StyleBouras, Ahmed, Souhir Guidara, Mélanie Leone, Adrien Buisson, Tanguy Martin-Denavit, Sophie Dussart, Christine Lasset, Sophie Giraud, Marie-Noëlle Bonnet-Dupeyron, Zine-Eddine Kherraf, and et al. 2023. "Overview of the Genetic Causes of Hereditary Breast and Ovarian Cancer Syndrome in a Large French Patient Cohort" Cancers 15, no. 13: 3420. https://doi.org/10.3390/cancers15133420