Abstract
Objectives: In silico splicing analysis, a mini-gene assay and splicing data, obtained using RNA from blood samples, have shown that the BRCA1 c.5332G > A variant induces exon 21 skipping. However, despite these evidences, up to date, this variant is unclassified. The aim of this study is to provide further molecular and clinical evidence for the BRCA1 c.5332G > A variant in a patient with high grade serous ovarian carcinoma (HGSOC) to allow a definitive classification of this variant. Design and method: The effect of the BRCA1 c.5332G > A variant on RNA splicing was evaluated by amplifying regions of BRCA1 from the cDNA of the patient. Loss of heterozygosity (LOH) in tumor tissue was also investigated. Results: The c.5332G > A allele causes significantly aberrant splicing of the BRCA1 exon 21. Evaluation of the c.5332A allele in tumor tissue highlights a possible loss of heterozygosity, supporting her pathogenic effect. Conclusions: Our results regarding the c.5332G > A variant confirm that it contributed to predisposition and onset of ovarian carcinoma in the patient. We propose to classify this variant as ‘likely-pathogenic’ (class IV).
| Original language | English |
|---|---|
| Pages (from-to) | 54-58 |
| Number of pages | 5 |
| Journal | Clinical Biochemistry |
| Volume | 63 |
| DOIs | |
| Publication status | Published - Jan 1 2019 |
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Keywords
- Exon skipping
- Hereditary ovarian cancer
- Loss of heterozygosity
- Splicing variant
ASJC Scopus subject areas
- Clinical Biochemistry
Cite this
Additional molecular and clinical evidence open the way to definitive IARC classification of the BRCA1 c.5332G > A (p.Asp1778Asn) variant. / Minucci, Angelo; Lalle, Maurizio; De Leo, Rossella; Mazzuccato, Giorgia; Scambia, Giovanni; Urbani, Andrea; Fagotti, Anna; Concolino, Paola; Capoluongo, Ettore.
In: Clinical Biochemistry, Vol. 63, 01.01.2019, p. 54-58.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Additional molecular and clinical evidence open the way to definitive IARC classification of the BRCA1 c.5332G > A (p.Asp1778Asn) variant
AU - Minucci, Angelo
AU - Lalle, Maurizio
AU - De Leo, Rossella
AU - Mazzuccato, Giorgia
AU - Scambia, Giovanni
AU - Urbani, Andrea
AU - Fagotti, Anna
AU - Concolino, Paola
AU - Capoluongo, Ettore
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Objectives: In silico splicing analysis, a mini-gene assay and splicing data, obtained using RNA from blood samples, have shown that the BRCA1 c.5332G > A variant induces exon 21 skipping. However, despite these evidences, up to date, this variant is unclassified. The aim of this study is to provide further molecular and clinical evidence for the BRCA1 c.5332G > A variant in a patient with high grade serous ovarian carcinoma (HGSOC) to allow a definitive classification of this variant. Design and method: The effect of the BRCA1 c.5332G > A variant on RNA splicing was evaluated by amplifying regions of BRCA1 from the cDNA of the patient. Loss of heterozygosity (LOH) in tumor tissue was also investigated. Results: The c.5332G > A allele causes significantly aberrant splicing of the BRCA1 exon 21. Evaluation of the c.5332A allele in tumor tissue highlights a possible loss of heterozygosity, supporting her pathogenic effect. Conclusions: Our results regarding the c.5332G > A variant confirm that it contributed to predisposition and onset of ovarian carcinoma in the patient. We propose to classify this variant as ‘likely-pathogenic’ (class IV).
AB - Objectives: In silico splicing analysis, a mini-gene assay and splicing data, obtained using RNA from blood samples, have shown that the BRCA1 c.5332G > A variant induces exon 21 skipping. However, despite these evidences, up to date, this variant is unclassified. The aim of this study is to provide further molecular and clinical evidence for the BRCA1 c.5332G > A variant in a patient with high grade serous ovarian carcinoma (HGSOC) to allow a definitive classification of this variant. Design and method: The effect of the BRCA1 c.5332G > A variant on RNA splicing was evaluated by amplifying regions of BRCA1 from the cDNA of the patient. Loss of heterozygosity (LOH) in tumor tissue was also investigated. Results: The c.5332G > A allele causes significantly aberrant splicing of the BRCA1 exon 21. Evaluation of the c.5332A allele in tumor tissue highlights a possible loss of heterozygosity, supporting her pathogenic effect. Conclusions: Our results regarding the c.5332G > A variant confirm that it contributed to predisposition and onset of ovarian carcinoma in the patient. We propose to classify this variant as ‘likely-pathogenic’ (class IV).
KW - Exon skipping
KW - Hereditary ovarian cancer
KW - Loss of heterozygosity
KW - Splicing variant
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U2 - 10.1016/j.clinbiochem.2018.10.004
DO - 10.1016/j.clinbiochem.2018.10.004
M3 - Article
VL - 63
SP - 54
EP - 58
JO - Clinical Biochemistry
JF - Clinical Biochemistry
SN - 0009-9120
ER -