scholarly journals How Far Do We Go With Genetic Evaluation? Gene, Panel, and Tumor Testing

2016 ◽  
pp. e72-e78 ◽  
Author(s):  
Filipa Lynce ◽  
Claudine Isaacs
Keyword(s):  
Cancer Susceptibility ◽  
Single Gene ◽  
Susceptibility Gene ◽  
Molecular Profiling ◽  
Brca1 And Brca2 ◽  
Management Options ◽  
Gene Testing ◽  
Number Of Genes ◽  
Targeted Testing ◽  
Hereditary Susceptibility

The traditional model by which an individual was identified as harboring a hereditary susceptibility to cancer was to test for a mutation in a single gene or a finite number of genes associated with a particular syndrome (e.g., BRCA1 and BRCA2 for hereditary breast and ovarian cancer or mismatch repair genes for Lynch syndrome). The decision regarding which gene or genes to test for was based on a review of the patient’s personal medical history and their family history. With advances in next-generation DNA sequencing technology, offering simultaneous testing for multiple genes associated with a hereditary susceptibility to cancer is now possible. These panels typically include high-penetrance genes, but they also often include moderate- and low-penetrance genes. A number of the genes included in these panels have not been fully characterized either in terms of their cancer risks or their management options. Another way some patients are unexpectedly identified as carrying a germline mutation in a cancer susceptibility gene is at the time they undergo molecular profiling of their tumor, which typically has been carried out to guide treatment choices for their cancer. This article first focuses on the issues that need to be considered when deciding between recommending more targeted testing of a single or a small number of genes associated with a particular syndrome (single/limited gene testing) versus performing a multigene panel. This article also reviews the issues regarding germline risk that occur within the setting of ordering molecular profiling of tumors.

scholarly journals Management Options after Prophylactic Surgeries in Women with BRCA Mutations: A Review

2007 ◽  
Vol 14 (4) ◽  
pp. 330-337 ◽  
Author(s):  
Dawn C. Allain ◽  
Kevin Sweet ◽  
Doreen M. Agnese
Keyword(s):  
Medical Management ◽  
Cancer Susceptibility ◽  
Brca Mutation ◽  
Brca2 Gene ◽  
Brca1 And Brca2 ◽  
Management Options ◽  
Cancer Susceptibility Genes ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Brca Mutation Carriers

Background Although breast cancer is relatively common, only about 5% of cases are due to inheritance of highly penetrant cancer susceptibility genes. The majority of these are caused by mutations in the BRCA1 and BRCA2 genes, which are also associated with an increased risk of ovarian cancer. Increased surveillance, chemoprevention, and prophylactic surgeries are standard options for the effective medical management of mutation carriers. However, optimal management of female carriers who choose to undergo prophylactic surgeries is still poorly understood. Methods The authors provide an overview of the current literature regarding medical management options for women carriers of BRCA1 and BRCA2 gene mutations and the implications for those individuals who have chosen to undergo prophylactic surgeries. Results BRCA mutation carriers who opt for prophylactic surgeries are still at risk for development of malignancy, and appropriate monitoring is warranted. Conclusions There are limited data on the appropriate medical management for BRCA mutation carriers after prophylactic surgeries. However, a management plan can be extrapolated from the general management recommendations for surveillance and other risk-reducing strategies in BRCA-positive individuals.

Germline cancer susceptibility gene testing in unselected patients with hepatobiliary cancers: A multi-center prospective study

2021 ◽  
pp. canprevres.0189.2021
Author(s):  
Pedro LS Uson Junior ◽  
Katie L Kunze ◽  
Michael A Golafshar ◽  
Douglas Riegert-Johnson ◽  
Lisa A Boardman ◽  
...  
Keyword(s):  
Prospective Study ◽  
Cancer Susceptibility ◽  
Susceptibility Gene ◽  
Gene Testing ◽  
Cancer Susceptibility Gene

Germline cancer susceptibility gene testing in unselected patients with colorectal adenocarcinoma: a multi-center prospective study

2021 ◽  
Vol 132 ◽  
pp. S34-S35
Author(s):  
Niloy Jewel Samadder ◽  
Pedro Serrano Uson ◽  
Douglas Riegert-Johnson ◽  
Lisa Boardman ◽  
Mitesh Borad ◽  
...  
Keyword(s):  
Prospective Study ◽  
Colorectal Adenocarcinoma ◽  
Cancer Susceptibility ◽  
Susceptibility Gene ◽  
Gene Testing ◽  
Cancer Susceptibility Gene

scholarly journals Direct detection of mutations in the breast and ovarian cancer susceptibility gene BRCA1 by PCR-mediated site-directed mutagenesis

1997 ◽  
Vol 43 (1) ◽  
pp. 24-29 ◽  
Author(s):  
Elizabeth M Rohlfs ◽  
William G Learning ◽  
Kenneth J Friedman ◽  
Fergus J Couch ◽  
Barbara L Weber ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Susceptibility ◽  
Direct Detection ◽  
Susceptibility Gene ◽  
Site Directed Mutagenesis ◽  
Base Substitution ◽  
Directed Mutagenesis ◽  
Wild Type ◽  
Brca1 And Brca2 ◽  
Pcr Products

Abstract The tumor suppressor genes BRCA1 and BRCA2, which confer increased susceptibility to breast and (or) ovarian cancer, were recently identified. Mutation analysis of BRCA1 has demonstrated significant allelic heterogeneity; however, some distinct mutations have been detected in unrelated individuals. The most notable is the 185delAG mutation, which occurs at an estimated frequency of ∼1% in individuals of Ashkenazi Jewish descent [1]. Although consensus has not been reached regarding clinical testing for mutations in BRCA1, a tiered strategy may be appropriate, in which direct testing for the more common mutations is one component. Specific alleles can be detected by using PCR-mediated site-directed mutagenesis (PSM), which alters the PCR products derived from either the wild-type or mutant allele to create or destroy a restriction endonuclease recognition site. Recognition sites are introduced by a base substitution in one of the primers. The alleles are then resolved by electrophoresis of the digested PCR products. We have applied this technique to the detection of four BRCA1 mutations: 185delAG, 5382insC, E1250X, and R1443X. Another mutation, 1294del40, can be resolved from the wild-type allele by high-resolution gel electrophoresis alone. The PSM technique is sensitive, does not require radioactivity, and is specific for individual mutations.

Laboratory Determination of Hereditary Susceptibility to Breast and Ovarian Cancer

1999 ◽  
Vol 123 (11) ◽  
pp. 1023-1026
Author(s):  
Tom S. Frank
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Prophylactic Surgery ◽  
Ovarian Cancer Risk ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Management Options ◽  
Increased Risk ◽  
Hereditary Susceptibility ◽  
Risk Of Cancer

Abstract Inherited mutations in the genes BRCA1 and BRCA2 are associated with a significantly increased risk of breast cancer, particularly before the age of 50 years, as well as an increased risk of ovarian cancer. Patients with early-onset breast cancer or ovarian cancer at any age with a family history of either disease are at higher risk of carrying a mutation in BRCA1 or BRCA2. Laboratory analysis of these genes can determine whether a patient has inherited an increased risk of breast and ovarian cancer. In the absence of a mutation that has been previously identified in a family member, most tests for hereditary breast-ovarian cancer risk analyze the entire coding sequences of BRCA1 and BRCA2. The gene sequencing process itself can be automated, but the data must be interpreted by an individual with training in molecular diagnostics. Management options generally available to individuals with hereditary susceptibility to breast and ovarian cancer include heightened surveillance, prophylactic surgery, and chemoprevention. The use of genetic techniques to identify women with increased risk of cancer demonstrates the application of recent advances in the understanding of the genetic basis of malignancy to laboratory medicine and clinical care.

scholarly journals PALB2 is an integral component of the BRCA complex required for homologous recombination repair

2009 ◽  
Vol 106 (17) ◽  
pp. 7155-7160 ◽  
Author(s):  
Shirley M. H. Sy ◽  
Michael S. Y. Huen ◽  
Junjie Chen
Keyword(s):  
Homologous Recombination ◽  
Cancer Susceptibility ◽  
Specific Interaction ◽  
Susceptibility Gene ◽  
Biological Significance ◽  
Direct Interaction ◽  
Breast Cancer Susceptibility Gene ◽  
Dna Breaks ◽  
Brca1 And Brca2

Mutations in breast cancer susceptibility gene 1 and 2 (BRCA1 and BRCA2) predispose individuals to breast and ovarian cancer development. We previously reported an in vivo interaction between BRCA1 and BRCA2. However, the biological significance of their association is thus far undefined. Here, we report that PALB2, the partner and localizer of BRCA2, binds directly to BRCA1, and serves as the molecular scaffold in the formation of the BRCA1-PALB2-BRCA2 complex. The association between BRCA1 and PALB2 is primarily mediated via apolar bonding between their respective coiled-coil domains. More importantly, BRCA1 mutations identified in cancer patients disrupted the specific interaction between BRCA1 and PALB2. Consistent with the converging functions of the BRCA proteins in DNA repair, cells harboring mutations with abrogated BRCA1-PALB2 interaction resulted in defective homologous recombination (HR) repair. We propose that, via its direct interaction with PALB2, BRCA1 fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Our findings uncover PALB2 as the molecular adaptor between the BRCA proteins, and suggest that impaired HR repair is one of the fundamental causes for genomic instability and tumorigenesis observed in patients carrying BRCA1, BRCA2, or PALB2 mutations.

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