Skip to main content

Advertisement

Table 3 BRCA mutations in cytological samples. All patients were previously tested for germline mutations from DNA extracted from the peripheral blood samples

From: Cytology material is equivalent to tumor tissue in determining mutations of BRCA 1/2 genes in patients with tubo-ovarian high grade serous carcinoma

Sample No. % of TC in the sample Gene Mutation AF in CS Germline vs. somatic mutation i,j Classification BICb HGMDc UMDd LOVDe ClinVarf
HGVS c.DNAa
HGVS proteina
1 70–80% BRCA1 c.844_850dupT CATTAC h p.(Gln284Leufs*5) 41% germline pathogenic CI DM C AfF P
2 90% BRCA1 c.116G > A h p.(Cys39Tyr) 97% germline pathogenic UV DM / AfF P
3 70% BRCA1 deletion of exons 4–9g
c.(134 + 1_135–1)_(670 + 1_671–1)del p.?
85% germline pathogenic / DM / / /
4 80% BRCA1 c.1543G > T h p.(Glu515*) 83% somatic pathogenic / / / / P
5 10% BRCA1 c.3018_3021delTTCA h p.(His1006Glnfs*17) 48% germline pathogenic CI DM C / P
6 30% BRCA1 c.1687C > T h p.(Gln563*) 53% germline pathogenic CI DM C AfF P
7 90% BRCA1 c.850C > T h p.(Gln284*) 94% germline pathogenic / DM / / P
8 70–60% BRCA1 deletion of exons 4–9g
c.(134 + 1_135–1)_(670 + 1_671–1)del p.?
80% germline pathogenic / DM / / /
9 30–40% BRCA2 c.4139_4140dupTT h p.(Lys1381Leufs*8) 55% germline pathogenic / DM / / P
10 80% BRCA1 c.843_846delCTCA h p.(Ser282Tyrfs*15) 93% Germline pathogenic CI DM C AfF P
11 60% BRCA1 c.843_846delCTCA h p.(Ser282Tyrfs*15) 84% germline pathogenic CI DM C AfF P
12 > 95% BRCA2 deletion of exons 22–27g
c.(8754 + 1_8755–1)_(*1_?)del p.?
80% somatic pathogenic / DM / / /
13 50% BRCA1 c.843_846delCTCA h p.(Ser282Tyrfs*15) 81% germline pathogenic CI DM C AfF P
14 1–3% BRCA1 c.1687C > T h p.(Gln563*) 51% germline pathogenic CI DM C AfF P
15 < 10% BRCA1 c.3436_3439delTGTT h p.(Cys1146Leufs*8) 43% germline pathogenic / DM C / P
16 20% BRCA1 c.844_850dupTCATTAC h p.(Gln284Leufs*5) 46% germline pathogenic CI DM C AfF P
17 40% BRCA1 c.4065_4068delTCAA h p.(Asn1355Lysfs*10) 54% germline pathogenic CI DM / UV P
  1. aThe description of nucleotide sequence variations is in accordance with HGVS nomenclature. DNA variants are numerated according to NCBI reference sequence NM_007294.3 for BRCA1 and NM_000059.3 for BRCA2. First nucleotide of start codon ATG is numerated as 1
  2. b https://research.nhgri.nih.gov/bic/
  3. c https://portal.biobase-international.com/
  4. dhttp://www.umd.be/BRCA1/ and http://www.umd.be/brca2/
  5. ehttps://lovd.nl/BRCA1 and https://lovd.nl/BRCA2
  6. f https://www.ncbi.nlm.nih.gov/clinvar/
  7. gAll large deletions were confirmed by MLPA analysis in cytological and tumor sample
  8. hAll SNV as well as indel were confirmed by Sanger sequencing in blood samples in case of germline mutations, and in cytological and tumor samples in case of somatic mutation
  9. iMutations were defined as germline, when they were detected in patients blood sample with mutation allele frequencies > 45%
  10. jMutations were defined as somatic, when detected in FFPE tumor samples and CF samples and not detected in patients blood sample
  11. TC-tumor cells, AF-allele frequency in the sample, CS-cytological sample, P-pathogenic, CI-clinically important, DM-disease causing mutation, C-casual, AfF-affects function, UV-unknown