Germline Mutations in <i>BRCA1 </i> and <i> BRCA2 </i> in  Breast-Ovarian Families From a Breast Cancer  Risk Evaluation Clinic

Martin, Anne‐Marie; Blackwood, M. Anne; Antin‐Ozerkis, Danielle; Shih, Helen A.; Calzone, Kathleen A.; Colligon, Theresa A.; Seal, Sheila; Collins, Nadine; Stratton, Michael R.; Weber, Barbara; Nathanson, K. L.

doi:10.1200/jco.2001.19.8.2247

Cited by 78 publications

(53 citation statements)

References 21 publications

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“…In keeping with what has been reported by others, 19,33 breast-ovarian cancer families were more likely to carry deleterious BRCA1/2 mutations than breast carcinoma-only families in our series. We also found good correlation between the likelihood of finding a deleterious mutation and genetic risk categories.…”

Section: Discussionsupporting

confidence: 79%

Utilization of BRCA1/2 genetic testing in the clinical setting

Lee

Bernhardt

Helzlsouer

2002

Cancer

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Heutzutage findet sich nur selten eine Ausgabe einer wichtigen Chemiezeitschrift, die nicht mindestens einen Artikel über die Festphasensynthese enthält. Das überrascht kaum, denn dieses Verfahren verspricht das Ende mühsamer Aufarbeitungen und die leichtere Herstellung riesiger Substanzbibliotheken mit kombinatorischen Methoden. Die Festphasentechnik ist inzwischen nicht mehr nur für die Peptidsynthese interessant: Mittlerweile gelang die Herstellung und Isolierung von zahlreichen Substanzklassen durch Festphasensynthese. Dieser Aufsatz beschäftigt sich mit dem „Linker“, der Ankergruppe zwischen polymerem Träger und Zielmolekül. Am Ende einer Synthese besteht die Aufgabe des Linkers darin, ein Produkt vom Träger in die Lösung freizusetzen: Dies geschieht ausnahmslos durch eine chemische Veränderung des Produkts an der vorherigen Verknüpfungsstelle. Einige Linker sind offenbar „spurlos“. Aber was genau ist „Spurlosigkeit“? Vor zwanzig Jahren, als die Spaltung eines Linkers eine polare Carbonsäure als Überrest (Spur) am Träger hinterließ, war diese Vorstellung sehr attraktiv. Heute stehen dem Chemiker zahllose neue Linker zur Verfügung, die Produkte mit den meisten Hauptfunktionalitäten an der früheren Verknüpfungsstelle abspalten können, und wir wollen zeigen, dass der Begriff „spurlos“ zwar derzeit weit verbreitet, aber ohne Bedeutung ist. Stattdessen schlagen wir eine Neuordnung der Linker vor, die sich nach den bei der Spaltung frei werdenden funktionellen Gruppen richtet, und empfehlen eine Nomenklatur, um diese Einteilung zu untermauern. Wir hoffen, mit diesem Aufsatz auch Gebiete der Linkertechnik hervorzuheben, die weiterer Forschung bedürfen.

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Section: Discussionsupporting

confidence: 79%

Utilization of BRCA1/2 genetic testing in the clinical setting

Lee

Bernhardt

Helzlsouer

2002

Cancer

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“…Mutations of the BRCA1 and BRCA2 genes are responsible for about 15 -40% of the breast cancer with familial aggregation and for the majority of hereditary ovarian cancer families. 1,2 Although initial data from the Linkage Consortium Study indicated a probability of 85% to develop breast cancer in a woman with BRCA gene mutation, 3,4 more recent studies suggest that the penetrance of BRCA1/2 mutations might be lower in non-highrisk families (Antoniou et al 5 and references therein). In the Italian population, the probability to develop a breast or an ovarian cancer at age 70 years was estimated to be 39 or 43%, respectively, for a BRCA1 mutation carrier and 44 and 15% for a BRCA2 mutation carrier.…”

Section: Introductionmentioning

confidence: 99%

Improving the accuracy of BRCA1/2 mutation prediction: validation of the novel country-customized IC software

et al. 2005

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Inherited mutations of the BRCA1/2 genes confer a significantly increased risk for breast and/or ovarian cancer development. Several models were elaborated to help genetic counsellors in selecting individuals with high probability of being mutation carriers. The IC software, a country-customized version of the Brcapro model, was recently shown to be particularly accurate in the prediction of carrier probability status in the Italian population. Here, we used our independent series of 70 breast/ovarian cancer families to analyze the performances of the IC software and compare it to widely used models, such as Brcapro and the Myriad mutation prevalence tables. Analysis of the areas under the receiver operator characteristics (ROC) curves indicated that overall the models performed well. However, the IC software and Myriad tables were more efficient in predicting mutated cases, showing a higher sensitivity (94 and 88%, respectively) and negative predictive value (NPV, 94 and 92%, respectively) compared to Brcapro (sensitivity 71 and NPV 83%). IC software also appeared particularly accurate in the identification of families belonging the low mutation risk group (o10%). Finally, most Brcapro failures occurred in the hereditary breast cancer (HBC) family subset, and in 75% of the cases, the IC software corrected them. Our data suggest that the country-customized implementation operated on the Brcapro software generated a more accurate tool for the prediction of BRCA1/2 gene mutation. Whether the IC or other countrycustomized models might improve BRCA1/2 mutation prediction also in non-Italian families needs to be further explored.

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“…Key words: BRCA1, breast cancer, ovarian cancer. The Breast Cancer Linkage Consortium dataset indicates that the proportion of familial breast and ovarian cancers associated to BRCA1 or BRCA2 may be as high as 98% (Martin et al, 2001). Mutations in BRCA1 account for 45% of families with multiple cases of breast cancer and for at least 80% of families with early-onset breast and/or ovarian cancer (Miki et al, 1994).…”

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confidence: 99%

BRCA1 mutations in Brazilian patients

et al. 2004

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BRCA1 mutations are known to be responsible for the majority of hereditary breast and ovarian cancers in women with early onset and a family history of the disease. In this paper we present a mutational survey conducted in 47 Brazilian patients with breast/ovarian cancer, selected based on age at diagnosis, family history, tumor laterality, and presence of breast cancer in male patients. All 22 coding exons and intron-exon junctions were sequenced. Constitutional mutations were found in seven families, consisting of one insertion (insC5382) in exon 20 (four patients), one four base-pair deletion (3450-3453delCAAG) in exon 11 resulting in a premature stop codon (one patient), one transition (IVS17+2T > C) in intron 17 affecting a mRNA splicing site (one patient), and a C > T transition resulting in a stop-codon (Q1135X) in exon 11 (one patient). The identification of these mutations which are associated to hereditary breast and ovarian cancers will contribute to the characterization of the mutational spectrum of BRCA1 and to the improvement of genetic counseling for familial breast/ovarian cancer patients in Brazil. Key words: BRCA1, breast cancer, ovarian cancer. The Breast Cancer Linkage Consortium dataset indicates that the proportion of familial breast and ovarian cancers associated to BRCA1 or BRCA2 may be as high as 98% (Martin et al., 2001). Mutations in BRCA1 account for 45% of families with multiple cases of breast cancer and for at least 80% of families with early-onset breast and/or ovarian cancer (Miki et al., 1994). Moreover, 88% of families with at least four cases of early-onset breast cancer and one case of ovarian cancer are related to mutations in BRCA1 and BRCA2 (Unger et al., 2000). Furthermore, germ line BRCA1 or BRCA2 mutation carriers also have an increased risk of developing other cancers in prostate, stomach, colon, pancreas, fallopian tubes and uterus when compared to the general population (Offit, 1998;Brose et al., 2002). However, the alternative possibility of mutations in other, still unidentified susceptibility genes with low penetrance or chance clustering in families with multiple cases of breast/ovarian cancer without mutations in BRCA1 or BRCA2 remains to be determined.More than 800 different mutations were reported in BRCA1, and most of them are listed in the Breast Cancer Information Core (BIC -http://research.nhgri.nih.gov/bic/). Mutation carriers have an increased risk of developing breast cancer at different ages, with estimates of approximately 37% up to 40 years, 66% up to 55, 73% up to 70, and 82% over their entire lifetime (Hall et al., 1990;Brose et al., 2002). As for ovarian cancer, the risk was estimated to be 29% up to 50 years and 40% up to 70 years (Ford et al

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Germline Mutations in BRCA1 and BRCA2 in Breast-Ovarian Families From a Breast Cancer Risk Evaluation Clinic

Cited by 78 publications

References 21 publications

Utilization of BRCA1/2 genetic testing in the clinical setting

Utilization of BRCA1/2 genetic testing in the clinical setting

Improving the accuracy of BRCA1/2 mutation prediction: validation of the novel country-customized IC software

BRCA1 mutations in Brazilian patients

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