BRCA1 mutations in a selected series of breast/ovarian cancer patients.

Garvin, Alex M.; Spycher, M; Häner, M; Torhorst, J.; Müller, Hansjakob; Herrmann, Roland; Rochlitz, C.; Weber, Walter; Scott, Rodney J.

doi:10.1136/jmg.33.9.721

Cited by 7 publications

(3 citation statements)

References 12 publications

(3 reference statements)

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“…Figure 4 demonstrates this is the case for the previously characterised BRCA1 1611delC mutant. 14 EBV transformed cells harbouring the mutation were grown in the presence or absence of cycloheximide, an inhibitor of protein synthesis. Genomic DNA or cDNA was used as template to amplify codons 447-581 of BRCA1 and the PCR products were sequenced.…”

Section: Nonsense-mediated Mrna Decay Is Inhibited By Cycloheximidementioning

confidence: 99%

“…[12][13][14] In each case, the general strategy is the same: cDNA is used as PCR template for the 21 smaller exons containing 40% of the coding sequence, while the 3427 basepairs (60% of the coding sequence) of exon 11 are amplified from genomic DNA. BRCA1 is PCR-amplified in five or six overlapping segments of convenient size, and the entire gene is screened for truncating mutations by analysing the five or six PCR products by in vitro transcription/ translation and SDS-PAGE.…”

Section: Introductionmentioning

confidence: 99%

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A complete protein truncation test for BRCA1 and BRCA2

Garvin

1998

Eur J Hum Genet

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The protein truncation test (PTT) is currently the fastest method in general use for detecting previously unidentified mutations in tumor suppressor genes. Greater than three kilobases of coding sequence can be screened by one PCR reaction, one coupled in vitro transcription/translation reaction, and one lane on an SDS-PAGE gel. The 16 kb of BRCA1/2 coding sequence can be screened with nine overlapping segments. Since 90% of BRCA1/2 mutations result in a truncated protein product, the theoretical false negative rate for a BRCA1/2 PTT screen should be 10%. In practice the false negative rate is much higher, especially when cDNA is used as template. However, the actual false negative rate for a given screen will depend on the details of how the test is performed. Design of the overlapping segments, gel parameters, and nonsense mediated mRNA decay can all influence the effectiveness of the screen. BRCA1/2 screening by PTT can be optimised by considering these variables. Furthermore, nonsense-mediated mRNA decay can be inhibited by blocking protein synthesis with cycloheximide.

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Section: Nonsense-mediated Mrna Decay Is Inhibited By Cycloheximidementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A complete protein truncation test for BRCA1 and BRCA2

Garvin

1998

Eur J Hum Genet

View full text Add to dashboard Cite

show abstract

“…Exon 11 was subdivided into three segments of 925, 1460, and 1456 bp in size. Primers used for this analysis have been described elsewhere (Garvin et al, 1996). PCR amplification of the three segments was as follows: 200 ng genomic DNA was used as template in a 25 µl reaction volume using standard PCR conditions except that the primer concentration was 200 nM.…”

Section: Ptt Analysismentioning

confidence: 99%

German family study on hereditary breast and/or ovarian cancer: Germline mutation analysis of the BRCA1 gene

Hamann¹,

Brauch²,

Garvin³

et al. 1997

Genes Chromosom. Cancer

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Women harboring BRCA1 germline mutations carry an 85% lifetime risk of developing breast cancer and a 63% risk of ovarian cancer. In this first systematic study of familial breast and/or ovarian cancer in Germany we investigated 29 families for germline mutations in the BRCA1 gene. We identified mutations in three breast cancer families and in four breast-ovarian cancer families. The mutations include one missense mutation, one frameshift mutation, one splice mutation, and four nonsense mutations cosegregating with breast and/or ovarian susceptibility in five of ten (50%) families showing positive evidence of linkage to chromosome band 17q21 and in two of 19 (11%) families where linkage data was not available. Two apparently unrelated families carried the same nonsense mutation at codon 1835 and three families harbored a C to T transition at nucleotide 49 of the untranslated exon 4. Allelotyping of the markers D17S855, D17S1322, D17S1323, and D17S1327 located within or near BRCA1 revealed that all affected individuals in the two families harboring the mutation at codon 1835 shared at least one allele indicating a founder mutation. With respect to the overall mutation spectrum, no mutations were identified in exon 11 (0/7) in this set of German families. These findings differed significantly from those in British (17/32)(P = 0.012) and Southern Swedish (13/15) (P < 0.001) families. The lack of BRCA1 mutations in exon 11 which represents 61% of the entire coding sequence may provide additional insight into BRCA1 associated breast and ovarian tumor development.

show abstract

German family study on hereditary breast and/or ovarian cancer: Germline mutation analysis of theBRCA1 gene

Hamann

Brauch²,

Garvin

et al. 1997

Genes Chromosom. Cancer

View full text Add to dashboard Cite

Women harboring BRCA1 germline mutations carry an 85% lifetime risk of developing breast cancer and a 63% risk of ovarian cancer. In this first systematic study of familial breast and/or ovarian cancer in Germany we investigated 29 families for germline mutations in the BRCA1 gene. We identified mutations in three breast cancer families and in four breast‐ovarian cancer families. The mutations include one missense mutation, one frameshift mutation, one splice mutation, and four nonsense mutations cosegregating with breast and/or ovarian susceptibility in five of ten (50%) families showing positive evidence of linkage to chromosome band 17q21 and in two of 19 (11%) families where linkage data was not available. Two apparently unrelated families carried the same nonsense mutation at codon 1835 and three families harbored a C to T transition at nucleotide 49 of the untranslated exon 4. Allelotyping of the markers D17S855, D17S1322, D17S1323, and D17S1327 located within or near BRCA1 revealed that all affected individuals in the two families harboring the mutation at codon 1835 shared at least one allele indicating a founder mutation. With respect to the overall mutation spectrum, no mutations were identified in exon 11 (0/7) in this set of German families. These findings differed significant from those in British (17/32)(P = 0.012) and Southern Swedish (13/15) (P < 0.001) families. The lack of BRCA1 mutations in exon 11 which represents 61% of the entire coding sequence may provide additional insight into BRCA1 associated breast and ovarian tumor development. Genes Chromosom. Cancer 18:126–132, 1997. © 1997 Wiley‐Liss, Inc.

show abstract

BRCA1 mutations in a selected series of breast/ovarian cancer patients.

Cited by 7 publications

References 12 publications

A complete protein truncation test for BRCA1 and BRCA2

A complete protein truncation test for BRCA1 and BRCA2

German family study on hereditary breast and/or ovarian cancer: Germline mutation analysis of the BRCA1 gene

German family study on hereditary breast and/or ovarian cancer: Germline mutation analysis of theBRCA1 gene

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