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
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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
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Implications of the germline variants of DNA damage response genes detected by cancer precision medicine for radiological risk communication and cancer therapy decisions
Noriko Hosoya,Kiyoshi Miyagawa +1 more
TL;DR: In this paper, the clinical significance of the genetic variants of the important DNA damage response genes, including ATM and TP53, and discuss how they can apply current knowledge to the management of cancer patients and their relatives from a radiological point of view.
Journal ArticleDOI
Association of RAD51C germline mutations with breast cancer among Bahamians.
Maryam Bagherzadeh,Agata Szymiczek,Talia Donenberg,Raleigh Butler,Judith Hurley,Steven A. Narod,Mohammad R. Akbari +6 more
TL;DR: These data support increasing evidence that RAD51C mutations contribute to breast cancer susceptibility, although the impact may vary substantially from country to country.
Growing recognition of the role for rare missense substitutions in breast cancer
TL;DR: In this paper, it was shown that for some breast cancer susceptibility genes, a significant proportion of the burden of disease comes from rare missense substitutions, and therefore, ongoing efforts to identify new susceptibility genes should not ignore missense variation.
Journal ArticleDOI
Discovery of a Pathogenic Variant rs139379666 (p. P2974L) in ATM for Breast Cancer Risk in Chinese Populations
Xingyi Guo,Weiqiang Lin,Mengqiu Bai,Hongzhi Li,Wanqing Wen,Chenjie Zeng,Zhishan Chen,Jing He,Jianghua Chen,Qiuyin Cai,Jirong Long,Wei Hua Jia,Xiao-Ou Shu,Wei Zheng +13 more
TL;DR: The findings identified a novel mutation that disrupts ATM function, conferring to breast cancer risk, and showed that the risk allele may play a defected regulation role in the activity of the ATM structure.
Journal ArticleDOI
Inhibition of DNA damage response pathway using combination of DDR pathway inhibitors and radiation in treatment of acute lymphoblastic leukemia cells.
Maryam Katoueezadeh,Niloofar Pilehvari,Ahmad Fatemi,Gholamhossein Hassanshahi,Seyedeh Atekeh Torabizadeh +4 more
TL;DR: In this paper, the synergistic effects of these inhibitors with irradiation for the treatment of acute leukemia was assessed, and the synergies of these drugs were shown to be beneficial.
References
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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.
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