Maternal and paternal lineage double heterozygosity alteration in familial breast cancer: a first case report

Pilato, Brunella; Summa, Simona De; Danza, Katia; Lambo, Rossana; Paradiso, Angelo; Tommasi, Stefania

doi:10.1007/s10549-010-1125-3

Cited by 12 publications

(12 citation statements)

References 19 publications

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“…N312/2015). The analysis was carried out from DNA extracted from the blood of all patients except one, from whom DNA was extracted from ascites fluid, using the QiAmp DNA blood midi kit (Qiagen, Valencia, CA) and following the manufacturer's instructions (Tommasi et al, 2008;Pilato et al, 2010Pilato et al, , 2011Pilato et al, , 2014.…”

Section: Sample Selectionmentioning

confidence: 99%

“…All parameter sets of this plug-in are indicated in Table 1. All variants called by the NGS platform were confirmed by Sanger sequencing as previously described (Tommasi et al, 2008;Pilato et al, 2010Pilato et al, , 2011Pilato et al, , 2014. When the pools were imbalanced, all variants which were not called considering the hot spot file (no call) were investigated by Sanger sequencing.…”

Section: Detection Of Brca1 and Brca2 Variantsmentioning

confidence: 99%

“…The procedure was first tested on a training set of 40 control samples previously analyzed by Sanger sequencing, and then blindly validated on 72 consecutive new samples (validation set). The training set was composed of patients appropriately selected to simulate a real-world diagnostics scenario according to BRCA1 and BRCA2 mutation frequencies (Tommasi et al, 2008;Pilato et al, 2010Pilato et al, , 2011Pilato et al, , 2014. In fact, all mutations in the training set are the most representative of populations analyzed in our Institute.…”

Section: Brca1 and Brca2 Variants In The Training And In The Validatimentioning

confidence: 99%

“…Our institute could be considered a reference center of the Apulia Region in the diagnosis of breast and ovarian familial cancer predisposition, having enrolled in 10 years more than 400 index cases and almost 350 relatives (Tommasi et al, 2008;Pilato et al, 2010Pilato et al, , 2011Pilato et al, , 2014. Lately, with the advent of PARP inhibitor treatment, our institute was also involved in screening of patients who may be eligible for such a treatment.…”

Section: Brca1-2 Diagnostic Workflowmentioning

confidence: 99%

“…To date, direct Sanger sequencing is considered the gold standard for the mutational analysis of BRCA1 (5,592 bp) and BRCA2 (10,257 bp); however, because of their large sizes and the absence of hot spot mutations, significant time is required for the entire analysis (Bermejo-Perez et al, 2007;Tommasi et al, 2008;Marsh and Howell, 2010;Pilato et al, 2010Pilato et al, , 2011Pilato et al, , 2014. Furthermore, analysis of large genomic rearrangements of these genes was necessary in all patients lacking point mutations and/or small indels (Ewald et al, 2009;Sluiter and van Rensburg, 2011).…”

Section: Introductionmentioning

confidence: 99%

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BRCA1‐2 diagnostic workflow from next‐generation sequencing technologies to variant identification and final report

Pilato

Pinto

Summa

et al. 2016

Genes Chromosomes & Cancer

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The BRCA1-BRCA2 genes predispose to hereditary breast and ovarian cancer, and the germline and mutational status of these genes defines a target population that can benefit from PARP inhibitor treatments. To respond to the increasing number of BRCA1-BRCA2 tests, it is necessary to shift to high-throughput technologies that are reliable and less time consuming. Different methodological platforms are dedicated to this purpose with different approaches and algorithms for analysis. Our aim was to set up a cost-effective and low time-consuming BRCA1-BRCA2 mutation detection workflow using the Ion Torrent PGM technology. A retrospective cohort of 40 patients with familial breast/ovarian cancer previously tested by Sanger sequencing and a prospective cohort of 72 patients (validation set) were analyzed. The validation set included 64 patients affected by familial breast/ovarian cancer and eight sporadic ovarian cancer cases, who are potential candidates for PARPi treatments. A complete and standardized workflow easily usable and suitable in a certified laboratory has been proved and validated. This includes all steps from library preparation to the final report. The use of next-generation sequencing will be of benefit for patients enrolled in the genetic counseling process and, moreover, will enhance the process of selecting patients eligible for personalized treatments. © 2016 Wiley Periodicals, Inc.

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Section: Sample Selectionmentioning

confidence: 99%

Section: Detection Of Brca1 and Brca2 Variantsmentioning

confidence: 99%

Section: Brca1 and Brca2 Variants In The Training And In The Validatimentioning

confidence: 99%

Section: Brca1-2 Diagnostic Workflowmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

BRCA1‐2 diagnostic workflow from next‐generation sequencing technologies to variant identification and final report

Pilato

Pinto

Summa

et al. 2016

Genes Chromosomes & Cancer

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Multilocus Inherited Neoplasia Alleles Syndrome

et al. 2016

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Mendelian causes of inherited cancer susceptibility are mostly rare and characterized by variable expression and incomplete penetrance. Phenotypic variability may result from a range of causes including locus heterogeneity, allelic heterogeneity, genetic and environmental modifier effects, or chance. Another potential cause is the presence of 2 or more inherited cancer predisposition alleles in the same individual. Although the frequency of such occurrences might be predicted to be low, such cases have probably been underascertained because standard clinical practice has been to test candidate inherited cancer genes sequentially until a pathogenic mutation is detected. However, recent advances in next-generation sequencing technologies now provide the opportunity to perform simultaneous parallel testing of large numbers of inherited cancer genes. Herein we provide examples of patients who harbor pathogenic mutations in multiple inherited cancer genes and review previously published examples to illustrate the complex genotype-phenotype relationships in these cases. We suggest that clinicians should proactively consider the likelihood of this phenomenon (referred to herein as multilocus inherited neoplasia alleles syndrome [MINAS]) in patients with unusual inherited cancer syndrome phenotypes. To facilitate the clinical management of novel cases of MINAS, we have established a database to collect information on what is likely to be an increasingly recognized cohort of such individuals.

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Double heterozygosity for mutations in BRCA1 and BRCA2 in German breast cancer patients: implications on test strategies and clinical management

Heidemann

Fischer

Engel

et al. 2012

Breast Cancer Res Treat

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Double heterozygosity for disease-causing BRCA1 and BRCA2 mutations is a very rare condition in most populations. Here we describe genetic and clinical data of eight female double heterozygotes (DH) for BRCA1 and BRCA2 mutations found in a cohort of 8162 German breast/ovarian cancer families and compare it with the data of their single heterozygous relatives and of the index patients of the German Consortium for Hereditary Breast and Ovarian Cancer. Furthermore, we analyze the phenotypic features of these patients with respect to age at onset of first cancer, first breast/ovarian cancer and the number of disease manifestations and compare them to that of published Caucasian female DHs and their single heterozygous female relatives. German DHs were not significantly younger at diagnosis of first breast cancer than the single heterozygous index patients of the German Consortium. However, if the data of our study were pooled with that of the literature, DHs were substantially younger at onset of first cancer (mean age 40.4 years, 95 % CI = 36.6-44.1) than their single heterozygous female relatives (mean age 51.9 years, 95 % CI = 46.8-57.0). The two groups also differed concerning the onset of first breast cancer (mean age 40.6 years, 95 % CI = 36.6-44.5 vs. 52.6, 95 % CI = 47.5-57.6). In addition, DHs had a more severe disease than their female relatives carrying a single BRCA mutation (1.4 vs. 0.6 manifestations per person). In contrast to Ashkenazi Jewish females, Caucasian DH females might develop breast cancer at an earlier age and have a more severe disease than single heterozygous BRCA mutation carriers. Therefore, DHs may benefit from more intensive surveillance programs/follow-up care and prophylactic surgery.

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Maternal and paternal lineage double heterozygosity alteration in familial breast cancer: a first case report

Cited by 12 publications

References 19 publications

BRCA1‐2 diagnostic workflow from next‐generation sequencing technologies to variant identification and final report

BRCA1‐2 diagnostic workflow from next‐generation sequencing technologies to variant identification and final report

Multilocus Inherited Neoplasia Alleles Syndrome

Double heterozygosity for mutations in BRCA1 and BRCA2 in German breast cancer patients: implications on test strategies and clinical management

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