AMPLIFICATION OF SATELLITE DNA AT 16Q11.2 IN THE GERM-LINE OF A PATIENT WITH BREAST-CANCER

1994 ◽  
Author(s):  
L SAVELYEVA ◽  
B SCHNEIDER ◽  
LH FINKE ◽  
P SCHLAG ◽  
M SCHWAB
Keyword(s):  
Breast Cancer ◽  
Satellite Dna ◽  
Germ Line

scholarly journals Nucleotide sequences of highly repeated DNAs; compilation and comments

1982 ◽  
Vol 39 (1) ◽  
pp. 1-30 ◽  
Author(s):  
George L. Gabor Miklos ◽  
Amanda Clare Gill
Keyword(s):  
Satellite Dna ◽  
Germ Line ◽  
Sequence Data ◽  
Allelic Variation ◽  
Neutral Theory ◽  
Natural Populations ◽  
Evolutionary Significance ◽  
Nucleotide Sequence Data ◽  
A Genome ◽  
Repeated Dnas

SummaryThe nucleotide sequence data from highly repeated DNAs of inverte-brates and mammals are summarized and briefly discussed. Very similar conclusions can be drawn from the two data bases. Sequence complexities can vary from 2 bp to at least 359 bp in invertebrates and from 3 bp to at least 2350 bp in mammals. The larger sequences may or may not exhibit a substructure. Significant sequence variation occurs for any given repeated array within a species, but the sources of this heterogeneity have not been systematically partitioned. The types of alterations in a basic repeating unit can involve base changes as well as deletions or additions which can vary from 1 bp to at least 98 bp in length. These changes indicate that sequence per se is unlikely to be under significant biological constraints and may sensibly be examined by analogy to Kimura's neutral theory for allelic variation. It is not possible with the present evidence to discriminate between the roles of neutral and selective mechanisms in the evolution of highly repeated DNA.Tandemly repeated arrays are constantly subjected to cycles of amplification and deletion by mechanisms for which the available data stem largely from ribosomal genes. It is a matter of conjecture whether the solutions to the mechanistic puzzles involved in amplification or rapid redeployment of satellite sequences throughout a genome will necessarily give any insight into biological functions.The lack of significant somatic effects when the satellite DNA content of a genome is significantly perturbed indicates that the hunt for specific functions at the cellular level is unlikely to prove profitable.The presence or in some cases the amount of satellite DNA on a chromosome, however, can have significant effects in the germ line. There the data show that localized condensed chromatin, rich in satellite DNA, can have the effect of rendering adjacent euchromatic regions rec−, or of altering levels of recombination on different chromosomes. No data stemming from natural populations however are yet available to tell us if these effects are of adaptive or evolutionary significance.

The prevalence of germ-line TP53 mutations in women diagnosed with breast cancer before age 30

2009 ◽  
Vol 8 (4) ◽  
pp. 563-567 ◽  
Author(s):  
Ophira M. Ginsburg ◽  
Mohammad R. Akbari ◽  
Zeba Aziz ◽  
Robert Young ◽  
Henry Lynch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Germ Line ◽  
Tp53 Mutations

scholarly journals Searching for the missing genetic determinants of hereditary breast cancer risk by whole-exome sequencing of BRCA-negative patients: new candidate genes USP39, SLIT3, CREB3

2021 ◽  
Vol 67 (1) ◽  
pp. 111-116
Author(s):  
Kirill Zagorodnev ◽  
Aleksandr Romanko ◽  
Uliy Gorgul ◽  
Aleksandr Ivantsov ◽  
Anna Sokolenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Exome Sequencing ◽  
Candidate Genes ◽  
Whole Exome Sequencing ◽  
Hereditary Breast Cancer ◽  
Germ Line ◽  
Genetic Diagnosis ◽  
Clinical Signs ◽  
Causative Mutation ◽  
Whole Exome

The search for the new hereditary mutations and a precise molecular genetic diagnosis that determines the causative mutation in each specific case of hereditary breast cancer (BC) is a clinically important task since it helps to define the personal therapeutic approach and increase the effectiveness of preventive measures. Using whole-exome sequencing (WES) we analyzed the full spectrum of hereditary variations in 49 Russian patients with clinical signs of a hereditary disease which allowed us to compile a list of 229 candidate probably pathogenic germ-line variants. Then, the selected candidate mutations were validated by Sanger sequencing and molecular-epidemiological studies, the predisposing roles of three oncologically relevant mutations (USP39 c.*208G>C, SLIT3 p.Arg154Cys, and CREB3 p.Lys157Glu) were confirmed. Our candidate genes are first mentioned in connection with the hereditary risk of BC. The final proofs of the causative roles of these variants could be obtained through functional tests as well as via the analysis of the mutations segregation in BC families.

scholarly journals P4: CIRCULATING MIRNA PROFILES POINT TO DYSREGULATION IN TGFBETA/SMAD3 TUMOR SUPPRESSOR SIGNATURE IN BRCA POSITIVE BREAST CANCER PATIENTS

2016 ◽  
Vol 64 (3) ◽  
pp. 818.2-818
Author(s):  
I Shapira ◽  
T Bhuiya ◽  
S Arora ◽  
N Mukhi ◽  
S Datla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Real Time ◽  
Cancer Patients ◽  
Survival Data ◽  
Real Time Pcr ◽  
Germ Line ◽  
Germline Mutations ◽  
Breast Cancer Patients ◽  
Mean Differences

Purpose of StudyOver 240,000 individuals are diagnosed with breast cancer (BrCa) of which 12,000 individuals carry BRCA germline mutations. MicroRNA dysregulation is common in malignancy and may correlate with germline mutations.Aims:1. Analyze microRNAs in patients with breast cancer with or without BRCA germ line mutations, with and without cancer.2. Identify molecular BRCA mutant patients to deduct reasons for accelerated malignancy.Methods UsedWe analyzed plasma miR expression from 94 br cancer patients (41 BRCA positive) relative to 24 normal controls. All samples were collected between 2010 and 2014 and survival data was known for all cancer patients. TaqMan Open Array panel was used to simultaneously run hundreds of microRNA assays in the Applied Biosystem Open array real time PCR. Using AB open array real time PCR, 756 miRNA species were detected. Two-sample t-test was used for all 2-sample comparison and ANOVA followed by Tukey HSD post-hoc test to compare the miRs mean differences. All tests were 2-tailed and results with a p<0.05 were considered statistically significant.Summary of ResultsBRCA+underexpressed hsa-mir-10a and hsa-mir-376c and over-expressed Hsa- mir- 326 and Hsa-mir-143 relative to BRCA-; p<0.05.Using Coremine data mining linking genes and diseases differentially expressed circulating miRs are linked to tumor suppressor TGFbeta/SMAD3.ConclusionsThe early onset of breast cancer in BRCA mutant patients may recapitulate the pro-oncogenic effects of TGF-β. The context dependent SMAD3 binding & tumor suppression TGF-β effects are abrogated in BRCA mutant patients. TGF-β/Smad3 tumor-suppressor signature suppresses local inflammation in the tumor microenvironment.

scholarly journals Risk Estimation as a Decision-Making Tool for Genetic Analysis of the Breast Cancer Susceptibility Genes

1999 ◽  
Vol 15 (1-3) ◽  
pp. 53-65 ◽  
Author(s):  
Jenny Chang-Claude ◽  
Heiko Becher ◽  
Maria Caligo ◽  
Diana Eccles ◽  
Gareth Evans ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Familial Breast Cancer ◽  
Genetic Model ◽  
Germ Line ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Cancer Gene ◽  
Brca2 Mutations ◽  
Breast Cancer Gene

For genetic counselling of a woman on familial breast cancer, an accurate evaluation of the probability that she carries a germ-line mutation is needed to assist in making decisions about genetic-testing.We used data from eight collaborating centres comprising 618 families (346 breast cancer only, 239 breast or ovarian cancer) recruited as research families or counselled for familial breast cancer, representing a broad range of family structures. Screening was performed in affected women from 618 families for germ-line mutations in BRCA1 and in 176 families for BRCA2 mutations, using different methods including SSCP, CSGE, DGGE, FAMA and PTT analysis followed by direct sequencing. Germ-line BRCA1 mutations were detected in 132 families and BRCA2 mutations in 16 families. The probability of being a carrier of a dominant breast cancer gene was calculated for the screened individual under the established genetic model for breast cancer susceptibility, first, with parameters for age-specific penetrances for breast cancer only [7] and, second, with age-specific penetrances for ovarian cancer in addition [20]. Our results indicate that the estimated probability of carrying a dominant breast cancer gene gives a direct measure of the likelihood of detecting mutations in BRCA1 and BRCA2. For breast/ovarian cancer families, the genetic model according to Narod et al. [20] is preferable for calculating the proband's genetic risk, and gives detection rates that indicate a 50% sensitivity of the gene test. Due to the incomplete BRCA2 screening of the families, we cannot yet draw any conclusions with respect to the breast cancer only families.

Results of a population-based screening for hereditary breast cancer in a region of North-Central Italy: contribution of BRCA1/2 germ-line mutations

2007 ◽  
Vol 112 (2) ◽  
pp. 343-349 ◽  
Author(s):  
Ian J. Seymour ◽  
Silvia Casadei ◽  
Valentina Zampiga ◽  
Simonetta Rosato ◽  
Rita Danesi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hereditary Breast Cancer ◽  
Germ Line ◽  
Central Italy ◽  
Population Based ◽  
North Central ◽  
Germ Line Mutations

scholarly journals Cost-effectiveness analysis of germ-line BRCA testing in women with breast cancer and cascade testing in family members of mutation carriers

2018 ◽  
Vol 20 (9) ◽  
pp. 985-994 ◽  
Author(s):  
Haitham W Tuffaha ◽  
Andrew Mitchell ◽  
Robyn L Ward ◽  
Luke Connelly ◽  
James R G Butler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cost Effectiveness ◽  
Germ Line ◽  
Family Members ◽  
Cost Effectiveness Analysis ◽  
Brca Testing ◽  
Cascade Testing ◽  
Effectiveness Analysis ◽  
Mutation Carriers

scholarly journals Underdiagnosis of Hereditary Breast Cancer: Are Genetic Testing Guidelines a Tool or an Obstacle?

2019 ◽  
Vol 37 (6) ◽  
pp. 453-460 ◽  
Author(s):  
Peter D. Beitsch ◽  
Pat W. Whitworth ◽  
Kevin Hughes ◽  
Rakesh Patel ◽  
Barry Rosen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Germ Line ◽  
Test Results ◽  
Eligibility Criteria ◽  
Exact Test ◽  
Nccn Guidelines ◽  
Current Testing ◽  
Panel Testing ◽  
Pathogenic Variants

Purpose An estimated 10% of breast and ovarian cancers result from hereditary causes. Current testing guidelines for germ line susceptibility genes in patients with breast carcinoma were developed to identify carriers of BRCA1/ 2 variants and have evolved in the panel-testing era. We evaluated the capability of the National Comprehensive Cancer Network (NCCN) guidelines to identify patients with breast cancer with pathogenic variants in expanded panel testing. Methods An institutional review board–approved multicenter prospective registry was initiated with 20 community and academic sites experienced in cancer genetic testing and counseling. Eligibility criteria included patients with a previously or newly diagnosed breast cancer who had not undergone either single- or multigene testing. Consecutive patients 18 to 90 years of age were consented and underwent an 80-gene panel test. Health Insurance Portability and Accountability Act–compliant electronic case report forms collected information on patient demographics, diagnoses, phenotypes, and test results. Results More than 1,000 patients were enrolled, and data records for 959 patients were analyzed; 49.95% met NCCN criteria, and 50.05% did not. Overall, 8.65% of patients had a pathogenic/likely pathogenic (P/LP) variant. Of patients who met NCCN guidelines with test results, 9.39% had a P/LP variant. Of patients who did not meet guidelines, 7.9% had a P/LP variant. The difference in positive results between these groups was not statistically significant (Fisher’s exact test P = .4241). Conclusion Our results indicate that nearly half of patients with breast cancer with a P/LP variant with clinically actionable and/or management guidelines in development are missed by current testing guidelines. We recommend that all patients with a diagnosis of breast cancer undergo expanded panel testing.

scholarly journals Breast cancer in a patient with Birt-Hogg-Dubé syndrome (BHDS) with dramatic response to neoadjuvant chemotherapy

2020 ◽  
Vol 13 (2) ◽  
pp. e232226
Author(s):  
Vivek Yadala ◽  
Hassaan Jafri ◽  
Mary T Legenza ◽  
Maria Tirona
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Germ Line ◽  
Skin Lesions ◽  
Punch Biopsy ◽  
Bilateral Mastectomy ◽  
Invasive Mammary Carcinoma ◽  
Grade 3 ◽  
Brca1 Brca2 ◽  
Response To Neoadjuvant Chemotherapy

This is a case of 49-year-old white woman who presented with a rapidly growing right sided breast mass. A subsequent punch biopsy confirmed grade 3 invasive mammary carcinoma of no special type which was negative for oestrogen receptor, progesterone receptor and Her-2 neu overexpression. She was a carrier of folliculin gene mutation that is characteristic of Birt-Hogg-Dubé syndrome (BHDS), a condition known to cause skin lesions, renal cancers and pneumothoraces. Family history revealed patient’s mother, grandmother and maternal aunt developed renal cell carcinomas during their lifetime and were positive for the same germ line mutation. Tumour tissue was positive for TP53 mutation and negative for BRCA1, BRCA2 and other genes commonly associated with breast cancer. We report a patient with BHDS presenting with breast cancer that showed dramatic response to neoadjuvant chemotherapy prior to bilateral mastectomy, local chest wall radiation and 6 months of adjuvant capecitabine.

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