Detection of BRCA1 Mutations in Women With Early-Onset Ovarian Cancer by Use of the Protein Truncation Test

Lancaster, J.; Cj, Cochran; Ha, Brownlee; Ac, Evans; Berchuck, Andrew; Pa, Futreal; Rw, Wiseman

doi:10.1093/jnci/88.8.552

Cited by 14 publications

(8 citation statements)

References 10 publications

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“…Reaction products were then electrophoresed on 0.5 x MDE (FMC, ME, USA) gels, dried and autoradiographed. Additionally, BRCAI exon 11 and BRCA2 exons 10, 11 and 27 were screened for frameshift and nonsense mutations (producing premature stop codons) using the protein truncation test (PTT) (Lancaster et al, 1996a(Lancaster et al, , 1996b. Exon 11 (BRCAJ) and exons 10 and 27 (BRCA2) were amplified by PCR in one fragment, and exon 11 (BRCA2) in two fragments, in the presence of forward primers containing a T7 promoter and transcription/translation initiation sequence (primer sequences available from jmlanc@acpub.duke.edu).…”

Section: Methodsmentioning

confidence: 99%

BRCA1 and BRCA2 in breast cancer families from Wales: moderate mutation frequency and two recurrent mutations in BRCA1

et al. 1998

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(Miki et al, 1994;Wooster et al, 1995). Carriers of germline mutations in these genes are at increased risk of developing breast and ovarian cancers. Analysis of BRCA1/BRCA2 in high-risk families has demonstrated considerable heterogeneity in inactivating mutations, with a lower proportion of families attributable to mutations in either gene than had previously been predicted by statistical analyses (Castilla et al, 1994; Phelan et al, 1996;Serova et al, 1997). We have screened affected individuals from 17 high-risk Welsh breast and breast/ovarian cancer families for mutations in both BRCAJ and BRCA2 to determine the proportion of families attributable to defects in these genes. Recent experience with recurrent BRCAJ and BRCA2 mutations in the Ashkenazi Jewish and Icelandic populations (Neuhausen et al, 1996a;Offit et al, 1996;Thorlacius et al, 1996), coupled with studies of Welsh cystic fibrosis patients (Ashley, 1986;Cheadle et al, 1993;Lucotte and Hazout, 1995), suggests that screening for common genetic alterations in patients with familial breast and ovarian cancer in the Welsh population may prove a productive approach to the study of susceptibility in this group. PATIENTS AND METHODSSeventeen families with two or more individuals diagnosed with breast cancer before age 50 years and/or ovarian cancer were selected under informed consent from patients attending the

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Section: Methodsmentioning

confidence: 99%

BRCA1 and BRCA2 in breast cancer families from Wales: moderate mutation frequency and two recurrent mutations in BRCA1

et al. 1998

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“…Somatic mutations of BRCA1 and BRCA2 genes are very rare in sporadic cancers, although loss of heterozygosity (LOH) of the genomic regions encompassing these genes is not uncommon [45,46]. Despite the lack of somatic BRCA1 mutations in BLBCs, studies demonstrate that the BRCA1 pathway is dysfunctional in many sporadic BLBCs [38,39,47].…”

Section: Brca1 Pathway and Brcanessmentioning

confidence: 99%

Molecular heterogeneity of triple-negative breast cancer and its clinical implications

Irshad

Ellis

Tutt

2011

Current Opinion in Oncology

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“…However, subsequent to publication, additional sequence analysis revealed a frameshift mutation (nucleotide 2575delC) present in the same allele as P1637L (ref. 27; A. Futreal, personal communication). A second chromosome from an unrelated patient also has been discovered to contain both the frameshift mutation and P1637L, implying that P1637L is a rare polymorphism in linkage disequilibrium with the 2575delC frameshift mutation (ref.…”

Section: A Fusion Protein Containing Human Brca1 Inhibitsmentioning

confidence: 99%

“…A second chromosome from an unrelated patient also has been discovered to contain both the frameshift mutation and P1637L, implying that P1637L is a rare polymorphism in linkage disequilibrium with the 2575delC frameshift mutation (ref. 27; A. Futreal, personal communication). Modification of pAD-BRCA1-⌬2 by P1637L had no effect on the formation of small colonies ( Fig.…”

Section: A Fusion Protein Containing Human Brca1 Inhibitsmentioning

confidence: 99%

Human BRCA1 inhibits growth in yeast: Potential use in diagnostic testing

Humphrey

Salim

Erdos

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

111

106

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Germline-inactivating mutations of BRCA1 result in a hereditary predisposition to breast and ovarian cancer. Truncating mutations of BRCA1 predispose to cancer and can be ascertained by protein truncation testing or sequencing. However, cancer-predisposing missense mutations of BRCA1 are difficult to distinguish from polymorphisms by genetic testing methods currently used. Here we show that expression of BRCA1 or BRCA1 fused to a GAL4 activation domain in Saccharomyces cerevesiae inhibits growth, resulting in small colonies easily distinguishable from vectortransformed controls. The growth inhibitory effect can be localized to sequences encoding the recently described BRCA1 C-terminal domains. Growth suppression by a BRCA1 fusion protein is not inf luenced by introduction of neutral polymorphisms but is diminished or abolished by frameshift, nonsense, or disease-associated missense mutations located in the C-terminal 305 amino acids of BRCA1. These observations may permit the functional significance of many BRCA1 sequence changes to be assessed in yeast. Additionally, the correlation of growth suppression with wild-type forms of BRCA1 suggests that the assay may be capable of detecting functionally conserved interactions between the evolutionarily conserved BRCA1 C-terminal domains and cellular elements found in both human and yeast cells.Breast cancer is the second leading cause of cancer deaths among women in industrialized countries, and germline mutations of BRCA1 account for 2.5-5% of all cases of breast cancer (1). Women in high risk families who inherit inactivating mutations of BRCA1, a putative tumor suppressor gene, are currently estimated to have 87% and 44% lifetime risks for breast and ovarian cancer, respectively (2

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Detection of BRCA1 Mutations in Women With Early-Onset Ovarian Cancer by Use of the Protein Truncation Test

Cited by 14 publications

References 10 publications

BRCA1 and BRCA2 in breast cancer families from Wales: moderate mutation frequency and two recurrent mutations in BRCA1

BRCA1 and BRCA2 in breast cancer families from Wales: moderate mutation frequency and two recurrent mutations in BRCA1

Molecular heterogeneity of triple-negative breast cancer and its clinical implications

Human BRCA1 inhibits growth in yeast: Potential use in diagnostic testing

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