Mutation analysis of the MDM4 gene in German breast cancer patients.
Scarlett Reincke,Lina Govbakh,Bettina Wilhelm,Haiyan Jin,Natalia Bogdanova,Michael Bremer,Johann H. Karstens,Thilo Dörk +7 more
TLDR
There is no evidence for a major role of MDM4 coding variants in the inherited susceptibility towards breast cancer in German patients, and the resequencing study uncovered two new unclassified variants at a low frequency.Abstract:
MDM4 is a negative regulator of p53 and cooperates with MDM2 in the cellular response to DNA damage. It is unknown, however, whether MDM4 gene alterations play some role in the inherited component of breast cancer susceptibility. We sequenced the whole MDM4 coding region and flanking untranslated regions in genomic DNA samples obtained from 40 German patients with familial breast cancer. Selected variants were subsequently screened by RFLP-based assays in an extended set of breast cancer cases and controls. Our resequencing study uncovered two MDM4 coding variants in 4/40 patients. Three patients carried a silent substitution at codon 74 that was linked with another rare variant in the 5'UTR. No association of this allele with breast cancer was found in a subsequent screening of 133 patients with bilateral breast cancer and 136 controls. The fourth patient was heterozygous for the missense substitution D153G which is located in a less conserved region of the MDM4 protein but may affect a predicted phosphorylation site. The D153G substitution only partially segregated with breast cancer in the family and was not identified on additional 680 chromosomes screened. This study did not reveal clearly pathogenic mutations although it uncovered two new unclassified variants at a low frequency. We conclude that there is no evidence for a major role of MDM4 coding variants in the inherited susceptibility towards breast cancer in German patients.read more
Citations
More filters
Journal ArticleDOI
Targeting Mdmx to treat breast cancers with wild-type p53
Sue Haupt,D Buckley,Jia-Min B Pang,Jeffreena M Panimaya,Piotr J. Paul,Cristina Gamell,Elena A Takano,Y Ying Lee,Sanne Hiddingh,Toni-Maree Rogers,Amina F A S Teunisse,Marco J Herold,Jean-Christophe Marine,Stephen B. Fox,Aart G. Jochemsen,Ygal Haupt +15 more
TL;DR: It is proposed that Mdmx targeting is an attractive strategy for treating BrCas harboring wt p53, across a range of subtypes.
Journal ArticleDOI
Influence of MDM2 and MDM4 on development and survival in hereditary retinoblastoma
Adriana H. O. Reis,Ivna Néria Silva Ribamar de Carvalho,Paula Batista de Sousa Damasceno,Sima Ferman,Evandro Lucena,Jorge S. Lopez-Camelo,Héctor N. Seuánez,Fernando Regla Vargas +7 more
TL;DR: Retinoblastoma accounts for 3% of all childhood malignancies, with different incidences around the world, and results from loss‐of‐function of both RB1 alleles although other genes have been proposed to be involved in tumor development.
Journal ArticleDOI
The associations between MDM4 gene polymorphisms and cancer risk.
TL;DR: It is suggested that rs4245739 polymorphism in the MDM4 gene may play an important role in the etiology of cancer.
Journal ArticleDOI
MDM4 rs4245739 A > C polymorphism correlates with reduced overall cancer risk in a meta-analysis of 69477 subjects
Chaoyi Xu,Jinhong Zhu,Wen Fu,Zongwen Liang,Shujie Song,Yuan Zhao,Lihua Lyu,Anqi Zhang,Jing He,Ping Duan +9 more
TL;DR: The pooled results revealed that the MDM4 rs4245739C allele is associated with a decreased cancer risk in the heterozygous (AC vs. AA): ORs and 95% confidence intervals were used and the association was more prominent in Asians and population-based studies.
Journal ArticleDOI
Two novel cSNPs of weaver gene in Chinese indigenous goat and their associations with milk yield
Zhuanjian Li,Zhongqi Chen,Xianyong Lan,Liang Ma,Yujiao Qu,Yanli Liu,Mijie Li,Ping Wang,Fei Li,Hong Chen +9 more
TL;DR: The observation suggested that the allele “AsuII-A” had the positive effects on adjusted milk yield in the second lactation, and was identified and detected by MluI and AsuII forced PCR-RFLP in 1,019 Chinese indigenous goats.
References
More filters
Journal ArticleDOI
p53, the Cellular Gatekeeper for Growth and Division
TL;DR: The author regrets the lack of citations for many important observations mentioned in the text, but their omission is made necessary by restrictions in the preparation of review manuscripts.
Journal ArticleDOI
Live or let die: the cell's response to p53
Karen H. Vousden,Xin Lu +1 more
TL;DR: Understanding the complex mechanisms that regulate whether or not a cell dies in response to p53 will ultimately contribute to the development of therapeutic strategies to repair the apoptotic p53 response in cancers.
Journal ArticleDOI
A "Silent" Polymorphism in the MDR1 Gene Changes Substrate Specificity
Chava Kimchi-Sarfaty,Jung Mi Oh,In-Wha Kim,Zuben E. Sauna,Anna Maria Calcagno,Suresh V. Ambudkar,Michael M. Gottesman +6 more
TL;DR: It is hypothesized that the presence of a rare codon, marked by the synonymous polymorphism, affects the timing of cotranslational folding and insertion of P-gp into the membrane, thereby altering the structure of substrate and inhibitor interaction sites.
Journal ArticleDOI
Genome-wide association study identifies novel breast cancer susceptibility loci
Douglas F. Easton,Karen A. Pooley,Alison M. Dunning,Paul D.P. Pharoah,Deborah J. Thompson,Dennis G. Ballinger,Jeffery P. Struewing,Jonathan J. Morrison,Helen I. Field,Robert Luben,Nicholas J. Wareham,Shahana Ahmed,Catherine S. Healey,Richard Bowman,Kerstin B. Meyer,Christopher A. Haiman,Laurence K. Kolonel,Brian E. Henderson,Loic Le Marchand,Paul Brennan,Suleeporn Sangrajrang,Valerie Gaborieau,Fabrice Odefrey,Chen-Yang Shen,Pei-Ei Wu,Hui-Chun Wang,Diana Eccles,D. Gareth Evans,Julian Peto,Olivia Fletcher,Nichola Johnson,Sheila Seal,Michael R. Stratton,Nazneen Rahman,Georgia Chenevix-Trench,Georgia Chenevix-Trench,Stig E. Bojesen,Børge G. Nordestgaard,C K Axelsson,Montserrat Garcia-Closas,Louise A. Brinton,Stephen J. Chanock,Jolanta Lissowska,Beata Peplonska,Heli Nevanlinna,Rainer Fagerholm,H Eerola,Daehee Kang,Keun-Young Yoo,Dong-Young Noh,Sei Hyun Ahn,David J. Hunter,Susan E. Hankinson,David G. Cox,Per Hall,Sara Wedrén,Jianjun Liu,Yen-Ling Low,Natalia Bogdanova,Peter Schu¨rmann,Do¨rk Do¨rk,Rob A. E. M. Tollenaar,Catharina E. Jacobi,Peter Devilee,Jan G. M. Klijn,Alice J. Sigurdson,Michele M. Doody,Bruce H. Alexander,Jinghui Zhang,Angela Cox,Ian W. Brock,Gordon MacPherson,Malcolm W.R. Reed,Fergus J. Couch,Ellen L. Goode,Janet E. Olson,Hanne Meijers-Heijboer,Hanne Meijers-Heijboer,Ans M.W. van den Ouweland,André G. Uitterlinden,Fernando Rivadeneira,Roger L. Milne,Gloria Ribas,Anna González-Neira,Javier Benitez,John L. Hopper,Margaret R. E. McCredie,Margaret R. E. McCredie,Margaret R. E. McCredie,Melissa C. Southey,Melissa C. Southey,Graham G. Giles,Chris Schroen,Christina Justenhoven,Christina Justenhoven,Hiltrud Brauch,Hiltrud Brauch,Ute Hamann,Yon-Dschun Ko,Amanda B. Spurdle,Jonathan Beesley,Xiaoqing Chen,_ kConFab,Arto Mannermaa,Veli-Matti Kosma,Vesa Kataja,Jaana M. Hartikainen,Nicholas E. Day,David Cox,Bruce A.J. Ponder +109 more
TL;DR: To identify further susceptibility alleles, a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls was conducted, followed by a third stage in which 30 single nucleotide polymorphisms were tested for confirmation.
Related Papers (5)
Acetyl-CoA Carboxylase α Gene and Breast Cancer Susceptibility
Olga M. Sinilnikova,Sophie M. Ginolhac,Clémence Magnard,Mélanie Léoné,Olga Anczuków,Olga Anczuków,David J. Hughes,Karen Moreau,D Thompson,Christine Coutanson,Janet Hall,Pascale Romestaing,Jean-Pierre Gerard,Valérie Bonadona,Christine Lasset,David E. Goldgar,Virginie Joulin,Nicole Dalla Venezia,Gilbert M. Lenoir +18 more