Journal ArticleDOI
Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene
Alfons Meindl,Heide Hellebrand,Constanze Wiek,Verena Erven,Barbara Wappenschmidt,Dieter Niederacher,Marcel Freund,Peter Lichtner,Linda Hartmann,Heiner Schaal,Juliane Ramser,Ellen Honisch,Christian Kubisch,Hans Erich Wichmann,Karin Kast,Helmut Deissler,Christoph Engel,Bertram Müller-Myhsok,Kornelia Neveling,Marion Kiechle,Christopher G. Mathew,Detlev Schindler,Rita K. Schmutzler,Helmut Hanenberg,Helmut Hanenberg +24 more
Reads0
Chats0
TLDR
In index cases from 1,100 German families with gynecological malignancies, the first unambiguous evidence of highly penetrant mutations associated with human cancer in a RAD51 paralog is provided and support the 'common disease, rare allele' hypothesis.Abstract:
Germline mutations in a number of genes involved in the recombinational repair of DNA double-strand breaks are associated with predisposition to breast and ovarian cancer. RAD51C is essential for homologous recombination repair, and a biallelic missense mutation can cause a Fanconi anemia-like phenotype. In index cases from 1,100 German families with gynecological malignancies, we identified six monoallelic pathogenic mutations in RAD51C that confer an increased risk for breast and ovarian cancer. These include two frameshift-causing insertions, two splice-site mutations and two nonfunctional missense mutations. The mutations were found exclusively within 480 pedigrees with the occurrence of both breast and ovarian tumors (BC/OC; 1.3%) and not in 620 pedigrees with breast cancer only or in 2,912 healthy German controls. These results provide the first unambiguous evidence of highly penetrant mutations associated with human cancer in a RAD51 paralog and support the 'common disease, rare allele' hypothesis.read more
Citations
More filters
Dissertation
Impact of the 2014 NCCN guidelines for genetic testing on an academic gynecologic oncology practice
TL;DR: The referral rate for genetic counseling from January-March 2013 was determined to be 52% and in 2014 was 83.3%.
Journal ArticleDOI
Structural insights into BCDX2 complex function in homologous recombination
Yashpal Rawal,Li Jia,Aviv Meir,Hardeep Kaur,Eliza A. Ruben,Youngho Kwon,Kara A. Bernstein,Maria Jasin,Alexander B. Taylor,Sandeep Burma,Robert Hromas,Alexander V. Mazin,Weixing Zhao,Daohong Zhou,Elizabeth V. Wasmuth,Eric C. Greene,Patrick Sung,S. L. Olsen +17 more
Phoebe LeeYi-Ping FuJonine D. FigueroaLudmila Prokunina-OlssonJesus Gonzalez-Bosquet • Peter KraftZhaoming WangKevin B. JacobsMeredith YeagerMarie-Josephe Horner • Susan E. HankinsonAmy HutchinsonNilanjan ChatterjeeMontserrat Garcia-ClosasRegina G. Ziegler •
Robert N. Hoover,J. Chanock +1 more
TL;DR: It is concluded that rs999737 is an optimal tag SNP for common variants in the 14q24.1 region and thus narrow the candidate variants that should be investigated in follow-up laboratory evaluation.
Posted ContentDOI
Germline genetics encode the resistance, risk, and lymphatic metastasis of triple-negative breast cancer in the southern Chinese population
Mei Yang,Yanhui Fan,Qiangzu Zhang,Shunhua Han,Xiaoling Li,Teng Zhu,Min-Yi Cheng,Juntao Xu,Ci-Qiu Yang,Hong-Fei Gao,Zhang Chunming,Michael Q. Zhang,You-Qiang Song,Gang Niu,Kun Wang +14 more
TL;DR: The findings suggested that a health human genome could encode an ability fully protecting the individual from a persistent neoplastic threat.
References
More filters
Journal ArticleDOI
Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2.
TL;DR: Physical exercise and lack of obesity in adolescence were associated with significantly delayed breast cancer onset, and risks appear to be increasing with time.
Journal ArticleDOI
Biallelic Inactivation of BRCA2 in Fanconi Anemia
Niall G. Howlett,Toshiyasu Taniguchi,Susan B. Olson,Barbara Cox,Quinten Waisfisz,Christine E. M. de Die-Smulders,Nicole Persky,Markus Grompe,Hans Joenje,Gerard Pals,Hideyuki Ikeda,Edward A. Fox,Alan D. D'Andrea +12 more
TL;DR: It is shown that cell lines derived from FA-B and FA-D1 patients have biallelic mutations in BRCA2 and express truncated BRC a2 proteins, which may result in cancer risks similar to those observed in families withBRCA1 or BRCa2 mutations.
Journal ArticleDOI
Exomic Sequencing Identifies PALB2 as a Pancreatic Cancer Susceptibility Gene
Siân Jones,Siân Jones,Ralph H. Hruban,Mihoko Kamiyama,Michael Borges,Xiaosong Zhang,Xiaosong Zhang,D. Williams Parsons,D. Williams Parsons,Jimmy Lin,Jimmy Lin,Emily Palmisano,Kieran Brune,Elizabeth M. Jaffee,Christine A. Iacobuzio-Donahue,Anirban Maitra,Giovanni Parmigiani,Scott E. Kern,Victor E. Velculescu,Kenneth W. Kinzler,Bert Vogelstein,Bert Vogelstein,James R. Eshleman,Michael Goggins,Alison P. Klein +24 more
TL;DR: Through complete sequencing of the protein-coding genes in a patient with familial pancreatic cancer, a germline, truncating mutation in PALB2 was identified that appeared responsible for this patient's predisposition to the disease.
Journal ArticleDOI
Multifactorial Analysis of Differences Between Sporadic Breast Cancers and Cancers Involving BRCA1 and BRCA2 Mutations
Sunil R. Lakhani,Jocelyne Jacquemier,John P. Sloane,Barry A. Gusterson,Thomas J. Anderson,Marc J. van de Vijver,Linda M. Farid,Deon J. Venter,A C Antoniou,Amy Storfer-Isser,Elizabeth Smyth,C. Michael Steel,Neva E. Haites,Rodney J. Scott,David E. Goldgar,Susan L. Neuhausen,Peter A. Daly,Wilma Ormiston,Ross McManus,Siegfried Scherneck,Bruce A.J. Ponder,Debbie Ford,Julian Peto,Dominique Stoppa-Lyonnet,Yves-Jean Bignon,J. P. Struewing,Nigel K. Spurr,D. Timothy Bishop,J. G. M. Klijn,Peter Devilee,Cornelisse J. Cornelisse,Christine Lasset,Gilbert M. Lenoir,Rosa B. Barkardottir,Valgurdur Egilsson,Ute Hamann,Jenny Chang-Claude,Hagay Sobol,Barbara L. Weber,Michael R. Stratton,Douglas F. Easton +40 more
TL;DR: Key features of the histologic phenotypes of breast cancers in carriers of mutant BRCA1 and BRCa2 genes are identified and this information may improve the classification of breast cancer in individuals with a family history of the disease and may ultimately aid in the clinical management of patients.
Journal ArticleDOI
KORA--a research platform for population based health research.
TL;DR: The KORA infrastructure, aspects of data management and quality control, and the concept of cooperative research are presented.
Related Papers (5)
A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1
Yoshio Miki,Jeff Swensen,Donna M Shattuck-Eidens,P. Andrew Futreal,Keith D Harshman,Sean V. Tavtigian,Qingyun Liu,Charles Cochran,L. Michelle Bennett,Wei Ding,Russell Bell,Judith Rosenthal,Charles E. Hussey,Thanh Tran,Melody McClure,Cheryl Frye,Tom Hattier,Robert Phelps,Astrid Haugen-Strano,Harold Katcher,Kazuko Yakumo,Zahra Gholami,Daniel Shaffer,Steven Stone,Steven Bayer,Christian Wray,Robert Bogden,Priya Dayananth,John R. Ward,Patricia N. Tonin,Steven A. Narod,Pam K. Bristow,Frank H. Norris,Leah M. Helvering,Paul Morrison,Paul Robert Rosteck,Mei Lai,J. Carl Barrett,Cathryn M. Lewis,Susan L. Neuhausen,Lisa A. Cannon-Albright,David E. Goldgar,Roger W. Wiseman,Alexander Kamb,Mark H. Skolnick +44 more
Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies
Antonis C. Antoniou,Paul D.P. Pharoah,Steven A. Narod,Harvey A. Risch,Jorunn E. Eyfjord,John L. Hopper,Niklas Loman,Håkan Olsson,Oskar T. Johannsson,Åke Borg,Barbara Pasini,Paolo Radice,Siranoush Manoukian,Diana Eccles,Nelson L.S. Tang,E. Olah,Hoda Anton-Culver,Ellen Warner,Jan Lubinski,Jacek Gronwald,Bohdan Górski,Hrafn Tulinius,Steinunn Thorlacius,Hannaleena Eerola,Heli Nevanlinna,Kirsi Syrjäkoski,Olli Kallioniemi,Deborah J. Thompson,Christopher H. Evans,Julian Peto,Julian Peto,Fiona Lalloo,D G R Evans,Douglas F. Easton +33 more