Combined Tumor-Based BRCA1/2 and TP53 Mutation Testing in Ovarian Cancer
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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n = 237 Patients | |
---|---|
Median age at diagnosis (IQR) * | 62.0 (56.0–68.0) |
Histological type, n (%) | |
- High-grade serous carcinoma | 205 (86.5) |
- Low-grade serous carcinoma | 4 (1.7) |
- Clear-cell carcinoma | 2 (0.8) |
- Carcinosarcoma | 4 (1.7) |
- High-grade endometrioid carcinoma | 15 (6.3) |
- Undifferentiated carcinoma | 7 (3.0) |
FIGO stage, n (%) | |
- I | 8 (3.3) |
- II | 10 (4.2) |
- III | 126 (53.2) |
- IV | 45 (19.0) |
- NA | 48 (20.3) |
Type of samples, n (%) | |
- Biopsy | 93 (39.2) |
- Surgical samples | 127 (53.6) |
- NA | 17 (7.2) |
Sample collection, n (%) | |
- Primitive | 141 (59.4%) |
- Primitive post-neoadjuvant treatment | 62 (26.2%) |
- Relapse | 1 (0.4%) |
- Relapse post chemotherapy | 27 (11.4%) |
- NA | 6 (2.5%) |
Gene | Variant | Protein | Functional Domain | Variant Type | Germline | Allelic Frequency | LOH | TP53 Associated Mutation | Allelic Frequency |
---|---|---|---|---|---|---|---|---|---|
BRCA1 | c.134+3A>C | - | - | Splicing | No | 0.43 | Yes | c.375+1G>T | 0.45 |
BRCA1 | c.1121del | p.Thr374fs | - | Frameshift | Yes | 0.7 | Yes | c.394A>G; p.Lys132Glu | 0.63 |
BRCA1 | c.212+3A>G | - | Ring finger | Splicing | Yes | 0.85 | Yes | c.673-1G>C | 0.55 |
BRCA1 | c.1674del | p.Gly559Valfs*13 | - | Nonsense | Yes | 0.67 | Yes | c.742C>T; p.Arg248Trp | 0.57 |
BRCA1 | c.68_69del | p.Glu23fs | Ring finger + NES1 | Frameshift | Yes | 0.46 | Inconclusive | No | WT |
BRCA1 | c.190T>C | p.Cys64Arg | Ring finger | Missense | No | 0.19 | Yes | c.578A>T; p.His193Leu | 0.24 |
BRCA1 | c.5266dup | p.Gln1756_Asp1757fs | Linker | Frameshift | Yes | 0.77 | Yes | c.351del; p.Gly117fs | 0.29 |
BRCA1 | c.5468-2A>G | - | BRCT2/AD2 | Splicing | Yes | 0.50 | No | c.403T>C; p.Cys135Arg | 0.18 |
BRCA1 | c.5266dup | p.Gln1756_Asp1757fs | Linker | Frameshift | Yes | 0.74 | Yes | c.840A>C; p.Arg280Ser | 0.62 |
BRCA1 | c.514C>T | p.Gln172* | - | Nonsense | No | 0.04 | Yes | c.375+5del | 0.05 |
BRCA1 | c.81-1G>C | - | Ring finger + NES1 | Splicing | No | 0.14 | Yes | c.518T>C; p.Val173Ala | 0.09 |
BRCA2 | c.2612C>A | p.Ser871* | - | Nonsense | Yes | 0.89 | Yes | NR | NR |
BRCA1 | c.815_824dup | p.Gly275_Thr276fs | - | Frameshift | No | 0.69 | Yes | c.743G>A; p.Arg248Gln | 0.61 |
BRCA2 | c.6533_6542del | p.His2178Glnfs*10 | - | Deletion | No | 0.24 | Yes | c.1024C>T; p.Arg342Ter* | 0.29 |
BRCA1 | c.4183C>T | p.Gln1395* | Coil coiled/AD1 | Nonsense | Yes | 0.62 | Yes | c.527G>T; p.Cys176Phe | 0.44 |
BRCA1 | c.1789G>T | p.Glu597* | - | Nonsense | No | 0.16 | Yes | c.742C>T, p.Arg248Trp | 0.15 |
BRCA1 | c.3001G>T | p.Glu1001* | - | Nonsense | Yes | 0.68 | Yes | c.395A>G; p.Lys132Arg | 0.27 |
BRCA1 | c.5503C>T | p.Arg1835Stop | BRCT2/AD2 | Nonsense | Yes | 0.12 | Yes | c.395A>G; p.Lys132Arg | 0.20 |
BRCA1 | c.523A>T | p.Lys175* | - | Nonsense | No | 0.39 | No | c.614A>G; p.Tyr205Cys | 0.54 |
BRCA2 | c.7952del | p.Arg2651fs | Helical domain | Frameshift | No | 0.47 | Yes | c.681_682insT; p.Ser227_Asp228fs | 0.42 |
BRCA1 | c.4065_4068del | p.Asn1355fs | AD1 | Frameshift | Yes | 0.81 | Yes | c.824G>A; p.Cys275Tyr | 0.62 |
BRCA1 | c.2389G>T | p.Glu797* | - | Nonsense | No | 0.41 | Yes | c.586C>T; p.Arg196* | 0.26 |
BRCA2 | c.6591_6592del | p.Thr2197fs | - | Frameshift | Yes | 0.87 | Yes | NR | NR |
BRCA2 | c.2612C>A | p.Ser871* | - | Nonsense | No | 0.48 | No | c.394A>G; p.Lys132Glu | 0.15 |
BRCA2 | c.8487+1G>A | - | - | Splicing | No | 1 | Yes | No | WT |
BRCA2 | c.3785C>G | p.Ser1262* | - | Nonsense | Yes | 0.28 | Yes | c.1025G>A; p.Arg342Gln | 0.35 |
BRCA2 | c.2612C>A | p.Ser871* | - | Nonsense | Yes | 0.69 | Yes | c.524G>A; p.Arg175His | 0.42 |
BRCA1 | c.4658del | p.Leu1553fs | AD1 | Frameshift | Inconclusive | 0.87 | Yes | c.376-2A>G | 0.70 |
BRCA1 | c.3257T>G | p.Leu1086* | - | Nonsense | Yes | 0.55 | No | c.824G>A; p.Cys275Tyr | 0.22 |
BRCA1 | c.1063A>T | p.Lys355* | - | Nonsense | No | 0.61 | Yes | c.396G>T; p.Lys132Asn | 0.64 |
BRCA1 | c.3008_3009del | p.Phe1003fs | - | Frameshift | Yes | 0.80 | Yes | c.1010G>T; p.Arg337Leu | 0.52 |
BRCA1 | c.2679_2682del | p.Lys893fs | - | Frameshift | Yes | 0.63 | Yes | c.818 G>T; p.Arg273Leu | 0.48 |
BRCA2 | c.2492del | p.Val831fs | - | Frameshift | No | 0.21 | Yes | c.818G>T; p.Arg273Leu | 0.23 |
BRCA1 | c.4072G>T | p.Glu1358* | AD1 | Nonsense | No | 0.60 | Yes | c.403T>G; p.Cys135Gly | 0.62 |
BRCA1 | c.3995del | p.Gly1332fs | AD1 | Frameshift | No | 0.28 | Yes | c.783-1_784delinsCTT; p.? | 0.20 |
BRCA1 | c.4868C>G | p.Ala1623Gly | AD2 | Missense | No | 0.089 | Yes | c.644G>T, p.Ser215Ile | 0.0587 |
BRCA1 | c.4658del | p.Leu1553fs | AD1 | Frameshift | Yes | 0.87 | Yes | c.376-2A>G | 0.70 |
BRCA2 | c.5345_5346del | p.Gln1782fs | - | Frameshift | Yes | 0.66 | Yes | c.307_308insGAAAACCT; p.Tyr103_Gln104fs | 0.32 |
BRCA2 | c.3233_3234insT | p.Val1078_Ser1079fs | - | Frameshift | Yes | 0.76 | Yes | c.262del; p.Ala88fs | 0.68 |
BRCA2 | c.5682C>G | p.Tyr1894* | - | Nonsense | Yes | 0.91 | Yes | No | - |
BRCA2 | c.1834G>T | p.Glu612* | - | Nonsense | No | 0.04 | Yes | c.388C>T; p.Leu130Phe | 0.0294 |
BRCA2 | c.413_417del | - | Frameshift | No | 0.02 | Inconclusive | No | - | |
BRCA1 | Deletion exon 21 to 24 | p.? | - | Frameshift | Yes | 0.8 * | Yes | c.151del; p.Glu51fs | 0.52 |
TP53 Variant Type | Frequency |
---|---|
Missense | 102 (60%) |
Frameshift | 34 (20%) |
Nonsense | 20 (12%) |
Splicing | 13 (8%) |
Total | 169 |
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Borcoman, E.; Santana dos Santos, E.; Genestie, C.; Pautier, P.; Lacroix, L.; Caputo, S.M.; Cabaret, O.; Guillaud-Bataille, M.; Michels, J.; Auguste, A.; et al. Combined Tumor-Based BRCA1/2 and TP53 Mutation Testing in Ovarian Cancer. Int. J. Mol. Sci. 2023, 24, 11570. https://doi.org/10.3390/ijms241411570
Borcoman E, Santana dos Santos E, Genestie C, Pautier P, Lacroix L, Caputo SM, Cabaret O, Guillaud-Bataille M, Michels J, Auguste A, et al. Combined Tumor-Based BRCA1/2 and TP53 Mutation Testing in Ovarian Cancer. International Journal of Molecular Sciences. 2023; 24(14):11570. https://doi.org/10.3390/ijms241411570
Chicago/Turabian StyleBorcoman, Edith, Elizabeth Santana dos Santos, Catherine Genestie, Patricia Pautier, Ludovic Lacroix, Sandrine M. Caputo, Odile Cabaret, Marine Guillaud-Bataille, Judith Michels, Aurelie Auguste, and et al. 2023. "Combined Tumor-Based BRCA1/2 and TP53 Mutation Testing in Ovarian Cancer" International Journal of Molecular Sciences 24, no. 14: 11570. https://doi.org/10.3390/ijms241411570