keyword
MENU ▼
Read by QxMD icon Read
search

Brca2

keyword
https://www.readbyqxmd.com/read/28643177/targeting-dna-repair-and-replication-stress-in-the-treatment-of-ovarian-cancer
#1
REVIEW
Junko Murai
Approximately half of high-grade serous epithelial ovarian cancers incur alterations in genes of homologous recombination (BRCA1, BRCA2, RAD51C, Fanconi anemia genes), and the rest incur alterations in other DNA repair pathways at high frequencies. Such cancer-specific gene alterations can confer selective sensitivity to DNA damaging agents such as cisplatin and carboplatin, topotecan, etoposide, doxorubicin, and gemcitabine. Originally presumed to inhibit DNA repair, PARP inhibitors that have recently been approved by the FDA for the treatment of advanced ovarian cancer also act as DNA damaging agents by inducing PARP-DNA complexes...
June 22, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28643015/the-role-of-screening-mri-in-the-era-of-next-generation-sequencing-and-moderate-risk-genetic-mutations
#2
REVIEW
Sarah Macklin, Jennifer Gass, Ghada Mitri, Paldeep S Atwal, Stephanie Hines
With the advent of next-generation sequencing, the ability to rapidly analyze numerous genes simultaneously has led to the creation of large cancer gene panels. Some of these genes, like BRCA1 and BRCA2, have been heavily researched and have well-established management guidelines. Other more newly established genes, like ATM, CHEK2, and PALB2, have previously had less robust research surrounding them which has limited the ability to create accurate risk estimates. With their inclusion on gene panels, there has been more pressure to produce management guidelines for patients discovered to carry pathogenic variants in these genes...
June 22, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28642255/family-history-is-strong-risk-factor-in-brca1-and-brca2-carriers-study-finds
#3
Jacqui Wise
No abstract text is available yet for this article.
June 21, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28634224/igh-myc-translocation-associates-with-brca2-deficiency-and-synthetic-lethality-to-parp1-inhibitors
#4
Silvia Maifrede, Kayla Martin, Paulina Podszywalow-Bartnicka, Katherine Sullivan, Samantha K Langer, Reza Nejadi, Yashodhara Dasgupta, Michael Hulse, Daniel Gritsyuk, Margaret Nieborowska-Skorska, Lena N Lupey-Green, Huaqing Zhao, Katarzyna Piwocka, Mariusz A Wasik, Italo Tempera, Tomasz Skorski
Burkitt lymphoma/leukemia (BL) cells carry t(8;14)(q24;q32) chromosomal translocation encoding IGH/MYC, which results in the constitutive expression of the MYC oncogene. Here, it is demonstrated that untreated and cytarabine (AraC)-treated IGH/MYC-positive BL cells accumulate a high number of potentially lethal DNA double-strand breaks (DSBs) and display low levels of the BRCA2 tumor suppressor protein, which is a key element of homologous recombination (HR)-mediated DSB repair. BRCA2 deficiency in IGH/MYC-positive cells was associated with diminished HR activity and hypersensitivity to poly (ADP-ribose) polymerase-1 (PARP1) inhibitors (olaparib, talazoparib) used alone or in combination with cytarabine in vitro...
June 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28632866/risks-of-breast-ovarian-and-contralateral-breast-cancer-for-brca1-and-brca2-mutation-carriers
#5
Karoline B Kuchenbaecker, John L Hopper, Daniel R Barnes, Kelly-Anne Phillips, Thea M Mooij, Marie-José Roos-Blom, Sarah Jervis, Flora E van Leeuwen, Roger L Milne, Nadine Andrieu, David E Goldgar, Mary Beth Terry, Matti A Rookus, Douglas F Easton, Antonis C Antoniou, Lesley McGuffog, D Gareth Evans, Daniel Barrowdale, Debra Frost, Julian Adlard, Kai-Ren Ong, Louise Izatt, Marc Tischkowitz, Ros Eeles, Rosemarie Davidson, Shirley Hodgson, Steve Ellis, Catherine Nogues, Christine Lasset, Dominique Stoppa-Lyonnet, Jean-Pierre Fricker, Laurence Faivre, Pascaline Berthet, Maartje J Hooning, Lizet E van der Kolk, Carolien M Kets, Muriel A Adank, Esther M John, Wendy K Chung, Irene L Andrulis, Melissa Southey, Mary B Daly, Saundra S Buys, Ana Osorio, Christoph Engel, Karin Kast, Rita K Schmutzler, Trinidad Caldes, Anna Jakubowska, Jacques Simard, Michael L Friedlander, Sue-Anne McLachlan, Eva Machackova, Lenka Foretova, Yen Y Tan, Christian F Singer, Edith Olah, Anne-Marie Gerdes, Brita Arver, Håkan Olsson
Importance: The clinical management of BRCA1 and BRCA2 mutation carriers requires accurate, prospective cancer risk estimates. Objectives: To estimate age-specific risks of breast, ovarian, and contralateral breast cancer for mutation carriers and to evaluate risk modification by family cancer history and mutation location. Design, Setting, and Participants: Prospective cohort study of 6036 BRCA1 and 3820 BRCA2 female carriers (5046 unaffected and 4810 with breast or ovarian cancer or both at baseline) recruited in 1997-2011 through the International BRCA1/2 Carrier Cohort Study, the Breast Cancer Family Registry and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, with ascertainment through family clinics (94%) and population-based studies (6%)...
June 20, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28631178/recent-insights-into-the-molecular-basis-of-fanconi-anemia-genes-modifiers-and-drivers
#6
REVIEW
Ronald S Cheung, Toshiyasu Taniguchi
Fanconi anemia (FA), the most common form of inherited bone marrow failure, predisposes to leukemia and solid tumors. FA is caused by the genetic disruption of a cellular pathway that repairs DNA interstrand crosslinks. The impaired function of this pathway, and the genetic instability that results, is considered the main pathogenic mechanism behind this disease. The identification of breast cancer susceptibility genes (for example, BRCA1/FANCS and BRCA2/FANCD1) as being major players in the FA pathway has led to a surge in molecular studies, resulting in the concept of the FA-BRCA pathway...
June 19, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28630945/the-icr96-exon-cnv-validation-series-a-resource-for-orthogonal-assessment-of-exon-cnv-calling-in-ngs-data
#7
Shazia Mahamdallie, Elise Ruark, Shawn Yost, Emma Ramsay, Imran Uddin, Harriett Wylie, Anna Elliott, Ann Strydom, Anthony Renwick, Sheila Seal, Nazneen Rahman
Detection of deletions and duplications of whole exons (exon CNVs) is a key requirement of genetic testing. Accurate detection of this variant type has proved very challenging in targeted next-generation sequencing (NGS) data, particularly if only a single exon is involved. Many different NGS exon CNV calling methods have been developed over the last five years. Such methods are usually evaluated using simulated and/or in-house data due to a lack of publicly-available datasets with orthogonally generated results...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28630313/targeting-reactive-nitrogen-species-suppresses-hereditary-pancreatic-cancer
#8
Mo Li, Qian Chen, Teng Ma, Xiaochun Yu
Germline mutation of BRCA2 induces hereditary pancreatic cancer. However, how BRCA2 mutation specifically induces pancreatic tumorigenesis remains elusive. Here, we have examined a mouse model of Brca2-deficiency-induced pancreatic tumors and found that excessive reactive nitrogen species (RNS), such as nitrite, are generated in precancerous pancreases, which induce massive DNA damage, including DNA double-strand breaks. RNS-induced DNA lesions cause genomic instability in the absence of Brca2. Moreover, with the treatment of antioxidant tempol to suppress RNS, not only are DNA lesions significantly reduced, but also the onset of pancreatic cancer is delayed...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28627585/role-of-metadherin-in-estrogen-regulated-gene-expression
#9
Yujun Li, Jesus Gonzalez Bosquet, Shujie Yang, Kristina W Thiel, Yuping Zhang, Haitao Liu, Kimberly K Leslie, Xiangbing Meng
The disruption of estrogen signaling is widely associated with the development of breast, endometrial and ovarian cancers. As a multifunctional mediator of carcinogenesis, metadherin (MTDH)/astrocyte elevated gene-1 (AEG-1) overexpression has been associated with numerous types of cancer, with reported roles in tumor initiation, proliferation, invasion, metastasis and chemoresistance. At the molecular level, MTDH has been shown to interact with proteins that drive tumorigenesis, including nuclear factor-κB (NF-κB), promyelocytic leukaemia zinc finger (PLZF), BRCA2- and CDKN1A (p21Cip1/Waf-1/mda-6)-interacting protein α (BCCIPα) and staphylococcal nuclease and tudor domain containing 1 (SND1)...
June 13, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28626402/effect-of-the-combination-of-trabectedin-and-pegylated-liposomal-doxorubicin-in-a-brca2-mutation-carrier-with-recurrent-platinum-sensitive-ovarian-cancer
#10
María Jesús Rubio Pérez
INTRODUCTION: The current standard of care for ovarian cancer is optimal cytoreduction with adjuvant chemotherapy based on a platinum/taxane combination. Although the response rate to this therapy is high, most patients ultimately relapse. Response to second-line therapy and prognosis are linked to the platinum-free interval (PFI); when both improve, the PFI increases. As a result, there is an increasing interest in the PFI extension strategies including platinum-free combinations. CASE PRESENTATION: A 50-year-old postmenopausal woman presented with ovarian serous carcinoma with peritoneal carcinomatosis...
May 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28625311/cancers-de-l%C3%A2-ovaire-brca-mut%C3%A3-consultation-d%C3%A2-oncog%C3%A3-n%C3%A3-tique-et-prescription-des-inhibiteurs-de-parp
#11
Laurence Gladieff, Dominique Stoppa Lyonnet, Alain Lortholary, Alexandra Leary, Catherine Genestie, Isabelle Ray-Coquard
GENETIC COUNSELING AND PARP INHIBITORS PRESCRIPTION: Upon the availability of the PARP inhibitors in relapsed ovarian carcinoma, the pathways of the oncogenetic counseling were modified. Any research for a constitutional alteration of the BRCA1 and BRCA2 genes must be accompanied by an oncogenetic counseling. BRCA testing is recommended from the diagnosis to every woman with an ovarian or fallopian tube or peritoneum of high grade adenocarcinoma, whatever the age at the diagnosis and her family history. In case of sensitive relapse or potential inclusion in a clinical trial and in the absence of preliminary constitutional research, the oncogenetic counseling is organized according to a fast track pathway and a somatic analysis can be realized in parallel...
May 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28624978/preferences-for-breast-cancer-risk-reduction-among-brca1-brca2-mutation-carriers-a-discrete-choice-experiment
#12
Alexander Liede, Carol A Mansfield, Kelly A Metcalfe, Melanie A Price, Carrie Snyder, Henry T Lynch, Sue Friedman, Justyna Amelio, Joshua Posner, Steven A Narod, Geoffrey J Lindeman, D Gareth Evans
PURPOSE: Unaffected women who carry BRCA1 or BRCA2 mutations face difficult choices about reducing their breast cancer risk. Understanding their treatment preferences could help us improve patient counseling and inform drug trials. The objective was to explore preferences for various risk-reducing options among women with germline BRCA1/2 mutations using a discrete-choice experiment survey and to compare expressed preferences with actual behaviors. METHODS: A discrete-choice experiment survey was designed wherein women choose between hypothetical treatments to reduce breast cancer risk...
June 17, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28623073/commentary-on-biallelic-inactivation-of-brca2-in-platinum-sensitive-metastatic-castration-resistant-prostate-cancer-cheng-hh-pritchard-cc-boyd-t-nelson-ps-montgomery-b-eur-urol-jun-2016-69-6-992-5
#13
Stephen Freedland, William Aronson
Understanding the molecular underpinnings of sensitivity to specific therapies will advance the goal of precision medicine in prostate cancer (PCa). We identified 3 patients with metastatic castration-resistant PCa (mCRPC) who achieved an exceptional response to platinum chemotherapy (not first-line treatment for PCa), despite disease progression on prior standard therapies. Using targeted next-generation sequencing on the primary and metastatic tumors, we found that all 3 patients had biallelic inactivation of BRCA2, a tumor suppressor gene critical for homologous DNA repair...
June 13, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28623072/commentary-on-integrative-clinical-genomics-of-advanced-prostate-cancer-robinson-d-van-allen-em-wu-ym-schultz-n-lonigro-rj-mosquera-jm-montgomery-b-taplin-me-pritchard-cc-attard-g-beltran-h-abida-w-bradley-rk-vinson-j-cao-x-vats-p-kunju-lp-hussain-m-feng-fy
#14
Stephen J Freedland, William J Aronson
Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF...
June 13, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28623070/commentary-on-inherited-dna-repair-gene-mutations-in-men-with-metastatic-prostate-cancer-pritchard-cc-mateo-j-walsh-mf-de-sarkar-n-abida-w-beltran-h-garofalo-a-gulati-r-carreira-s-eeles-r-elemento-o-rubin-ma-robinson-d-lonigro-r-hussain-m-chinnaiyan-a-vinson
#15
Stephen J Freedland, William J Aronson
BACKGROUND: Inherited mutations in DNA-repair genes such as BRCA2 are associated with increased risks of lethal prostate cancer. Although the prevalence of germline mutations in DNA-repair genes among men with localized prostate cancer who are unselected for family predisposition is insufficient to warrant routine testing, the frequency of such mutations in patients with metastatic prostate cancer has not been established. METHODS: We recruited 692 men with documented metastatic prostate cancer who were unselected for family history of cancer or age at diagnosis...
June 13, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28620890/identification-and-characterization-of-a-new-brca2-rearrangement-in-an-italian-family-with-hereditary-breast-and-ovarian-cancer-syndrome
#16
Paola Concolino, Roberta Rizza, Karl Hackmann, Angelo Minucci, Giovanni Luca Scaglione, Maria De Bonis, Alessandra Costella, Cecilia Zuppi, Evelin Schrock, Ettore Capoluongo
INTRODUCTION: Many studies document the involvement of BRCA1/2 gene rearrangements in genetic predisposition to breast and ovarian cancer. Large genomic rearrangements (LGRs) of BRCA1 account for 0-27% of all disease-causing mutations in various populations, while LGRs in BRCA2 are rarer. Here, we describe a novel BRCA2 LGR, involving the duplication of exons 4-26, in an Italian family with hereditary breast and ovarian cancer (HBOC) syndrome. OBJECTIVE: Our purpose was to provide an effective characterization of this variant using a combination of different methods able to establish the exact breakpoints of the duplication...
June 15, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28619759/modelling-therapy-resistance-in-brca1-2-mutant-cancers
#17
Amy Dréan, Chris T Williamson, Rachel Brough, Inger Brandsma, Malini Menon, Asha Konde, Isaac Garcia-Murillas, Helen N Pemberton, Jessica Frankum, Rumana Rafiq, Nicholas Badham, James Campbell, Aditi Gulati, Nicholas C Turner, Stephen J Pettitt, Alan Ashworth, Christopher J Lord
Although PARP inhibitors target BRCA1 or BRCA2 mutant tumour cells, drug resistance is a problem. PARP inhibitor resistance is sometimes associated with the presence of secondary or "revertant" mutations in BRCA1 or BRCA2 Whether secondary mutant tumour cells are selected for in a Darwinian fashion by treatment is unclear. Furthermore, how PARP inhibitor resistance might be therapeutically targeted is also poorly understood. Using CRISPR-mutagenesis, we generated isogenic tumour cell models with secondary BRCA1 or BRCA2 mutations...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28619461/predictability-of-brca1-2-mutation-status-in-patients-with-ovarian-cancer-how-to-select-women-for-genetic-testing-in-middle-income-countries
#18
Natalia Teixeira, Simone Maistro, Maria Del Pilar Estevez Diz, Marian J Mourits, Jan C Oosterwijk, Maria Aparecida Koike Folgueira, Geertruida H de Bock
OBJECTIVES: To evaluate the accuracy of algorithms for predicting BRCA1/2 germ-line mutation carrier probability, and to identify factors that could improve their performance among Brazilian women with ovarian cancer (OC). STUDY DESIGN: In this cross-sectional study, we enrolled patients (unselected for family history of cancer) undergoing treatment or follow-up for OC in a single centre in Brazil. Clinical and demographic data, including family history of cancer, were obtained...
June 4, 2017: Maturitas
https://www.readbyqxmd.com/read/28617445/acquired-cross-linker-resistance-associated-with-a-novel-spliced-brca2-protein-variant-for-molecular-phenotyping-of-brca2-disruption
#19
Stefan Meyer, Adam Stevens, Roberto Paredes, Marion Schneider, Michael J Walker, Andrew J K Williamson, Maria-Belen Gonzalez-Sanchez, Stephanie Smetsers, Vineet Dalal, Hsiang Ying Teng, Daniel J White, Sam Taylor, Joanne Muter, Andrew Pierce, Chiara de Leonibus, Davy A P Rockx, Martin A Rooimans, Elaine Spooncer, Stacey Stauffer, Kajal Biswas, Barbara Godthelp, Josephine Dorsman, Peter E Clayton, Shyam K Sharan, Anthony D Whetton
BRCA2 encodes a protein with a fundamental role in homologous recombination that is essential for normal development. Carrier status of mutations in BRCA2 is associated with familial breast and ovarian cancer, while bi-allelic BRCA2 mutations can cause Fanconi anemia (FA), a cancer predisposition syndrome with cellular cross-linker hypersensitivity. Cancers associated with BRCA2 mutations can acquire chemo-resistance on relapse. We modeled acquired cross-linker resistance with an FA-derived BRCA2-mutated acute myeloid leukemia (AML) platform...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28616972/dss1-regulates-association-of-brh2-with-rad51
#20
Qingwen Zhou, William K Holloman
Brh2, the BRCA2 ortholog in the fungus Ustilago maydis, mediates delivery of Rad51 to DNA during the course of homology-directed DNA repair. Rad51 interacts with Brh2 through the highly conserved BRC element and through a second region termed CRE located at the extreme carboxy-terminus. Dss1, a small intrinsically unstructured protein that interacts with Brh2 is crucial for its activity in DNA repair, but the mechanism of this regulation is uncertain. In previous studies we found that Brh2 interaction with DNA was strongly modulated by association with Dss1...
June 15, 2017: Biochemistry
keyword
keyword
23196
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"