Rare key functional domain missense substitutions in MRE11A, RAD50, and NBN contribute to breast cancer susceptibility: Results from a Breast Cancer Family Registry case-control mutation-screening study

Breast Cancer Research

Volumn 16, Issue 3, 2014, Pages

  Damiola, Francesca ^a,b   Pertesi, Maroulio ^a   Oliver, Javier ^a   Le Calvez Kelm, Florence ^a   Voegele, Catherine ^a   Young, Erin L ^c   Robinot, Nivonirina ^a   Forey, Nathalie ^a   Durand, Geoffroy ^a   Vallée, Maxime P ^a   Tao, Kayoko ^c   Roane, Terrell C ^d   Williams, Gareth J ^e   Hopper, John L ^f,k   Southey, Melissa C ^f   Andrulis, Irene L ^g   John, Esther M ^h,j   Goldgar, David E ^c   Lesueur, Fabienne ^a,i   Tavtigian, Sean V ^c  

^a INTERNATIONAL AGENCY FOR RESEARCH ON CANCER   (France)

^b CENTRE LÉON BÉRARD   (France)

^c UNIVERSITY OF UTAH   (United States)

^d UNIVERSITY OF TEXAS AT AUSTIN   (United States)

^e LAWRENCE BERKELEY NATIONAL LABORATORY   (United States)

^f UNIVERSITY OF MELBOURNE   (Australia)

^g MOUNT SINAI HOSPITAL   (Canada)

^h CANCER PREVENTION INSTITUTE OF CALIFORNIA   (United States)

ⁱ INSERM U900   (France)

^j STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^k Seoul National University   (South Korea)

more..

Author keywords

[No Author keywords available]

Indexed keywords

NBN PROTEIN; NUCLEIC ACID BINDING PROTEIN; PROTEIN MRE 11A; RAD50 PROTEIN; UNCLASSIFIED DRUG; ATM PROTEIN; ATM PROTEIN, HUMAN; BRCA1 PROTEIN; BRCA1 PROTEIN, HUMAN; BRCA2 PROTEIN; BRCA2 PROTEIN, HUMAN; CELL CYCLE PROTEIN; CHECKPOINT KINASE 2; CHEK2 PROTEIN, HUMAN; DNA BINDING PROTEIN; ISOPROTEIN; MRE11A PROTEIN, HUMAN; NBN PROTEIN, HUMAN; NUCLEAR PROTEIN; POLYDEOXYRIBONUCLEOTIDE SYNTHASE; RAD50 PROTEIN, HUMAN;

ADULT; AFRICAN AMERICAN; ALLELE; ARTICLE; ASIAN; BIOINFORMATICS; BREAST CANCER; CANCER SUSCEPTIBILITY; CONTROLLED STUDY; DNA BINDING; EUROPEAN AMERICAN; EXON; GENE FREQUENCY; GENE SEQUENCE; GENETIC SCREENING; GENOTYPE PHENOTYPE CORRELATION; HIGH RESOLUTION MELTING ANALYSIS; HUMAN; INHERITANCE; MAJOR CLINICAL STUDY; MISSENSE MUTATION; NONSENSE MEDIATED MRNA DECAY; NUCLEOTIDE SEQUENCE; OPEN READING FRAME; PROTEIN STRUCTURE; RECOMBINATION REPAIR; REPRODUCTIVE FITNESS; SEQUENCE ALIGNMENT; SEQUENCE ANALYSIS; AMINO ACID SUBSTITUTION; BREAST TUMOR; CASE CONTROL STUDY; DNA REPAIR; DNA SEQUENCE; DOUBLE STRANDED DNA BREAK; FEMALE; GENETIC PREDISPOSITION; GENETICS; MIDDLE AGED;

ADULT; AMINO ACID SUBSTITUTION; ATAXIA TELANGIECTASIA MUTATED PROTEINS; BASE SEQUENCE; BRCA1 PROTEIN; BRCA2 PROTEIN; BREAST NEOPLASMS; CASE-CONTROL STUDIES; CELL CYCLE PROTEINS; CHECKPOINT KINASE 2; DNA BREAKS, DOUBLE-STRANDED; DNA REPAIR; DNA REPAIR ENZYMES; DNA-BINDING PROTEINS; FEMALE; GENE FREQUENCY; GENETIC PREDISPOSITION TO DISEASE; GENETIC TESTING; HUMANS; MIDDLE AGED; MUTATION, MISSENSE; NUCLEAR PROTEINS; PROTEIN ISOFORMS; SEQUENCE ALIGNMENT; SEQUENCE ANALYSIS, DNA;

EID: 84905731318     PISSN: 14655411     EISSN: 1465542X     Source Type: Journal    
DOI: 10.1186/bcr3669     Document Type: Article

References (69)

1. Genetic susceptibility. World Cancer Report 2008 2008, 183-184. Lyon: IARC Press, Boyle P, Levin B.
2. Michailidou K, Hall P, Gonzalez-Neira A, Ghoussaini M, Dennis J, Milne RL, Schmidt MK, Chang-Claude J, Bojesen SE, Bolla MK, Wang Q, Dicks E, Lee A, Turnbull C, Rahman N, Fletcher O, Peto J, Gibson L, Dos Santos Silva I, Nevanlinna H, Muranen TA, Aittomaki K, Blomqvist C, Czene K, Irwanto A, Liu J, Waisfisz Q, Meijers-Heijboer H, Adank M, van der Luijt RB, et al. Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet 2013, 45:353-361. 361e1-2.
3. Hollestelle A, Wasielewski M, Martens JW, Schutte M. Discovering moderate-risk breast cancer susceptibility genes. Curr Opin Genet Dev 2010, 20:268-276.
4. Williams GJ, Lees-Miller SP, Tainer JA. Mre11-Rad50-Nbs1 conformations and the control of sensing, signaling, and effector responses at DNA double-strand breaks. DNA Repair (Amst) 2010, 9:1299-1306.
5. Xiao Y, Weaver DT. Conditional gene targeted deletion by Cre recombinase demonstrates the requirement for the double-strand break repair Mre11 protein in murine embryonic stem cells. Nucleic Acids Res 1997, 25:2985-2991.
6. Luo G, Yao MS, Bender CF, Mills M, Bladl AR, Bradley A, Petrini JH. Disruption of mRad50 causes embryonic stem cell lethality, abnormal embryonic development, and sensitivity to ionizing radiation. Proc Natl Acad Sci U S A 1999, 96:7376-7381.
7. Zhu J, Petersen S, Tessarollo L, Nussenzweig A. Targeted disruption of the Nijmegen breakage syndrome gene NBS1 leads to early embryonic lethality in mice. Curr Biol 2001, 11:105-109.
8. Waltes R, Kalb R, Gatei M, Kijas AW, Stumm M, Sobeck A, Wieland B, Varon R, Lerenthal Y, Lavin MF, Schindler D, Dork T. Human RAD50 deficiency in a Nijmegen breakage syndrome-like disorder. Am J Hum Genet 2009, 84:605-616.
9. Uchisaka N, Takahashi N, Sato M, Kikuchi A, Mochizuki S, Imai K, Nonoyama S, Ohara O, Watanabe F, Mizutani S, Hanada R, Morio T. Two brothers with ataxia-telangiectasia-like disorder with lung adenocarcinoma. J Pediatr 2009, 155:435-438.
10. Regal JA, Festerling TA, Buis JM, Ferguson DO. Disease-associated MRE11 mutants impact ATM/ATR DNA damage signaling by distinct mechanisms. Hum Mol Genet 2013, 22:5146-5159.
11. van der Burgt I, Chrzanowska KH, Smeets D, Weemaes C. Nijmegen breakage syndrome. J Med Genet 1996, 33:153-156.
12. Bender CF, Sikes ML, Sullivan R, Huye LE, Le Beau MM, Roth DB, Mirzoeva OK, Oltz EM, Petrini JH. Cancer predisposition and hematopoietic failure in Rad50(S/S) mice. Genes Dev 2002, 16:2237-2251.
13. Zhang ZH, Yang LS, Huang F, Hao JH, Su PY, Sun YH. Current evidence on the relationship between two polymorphisms in the NBS1 gene and breast cancer risk: a meta-analysis. Asian Pac J Cancer Prev 2012, 13:5375-5379.
14. Heikkinen K, Karppinen SM, Soini Y, Makinen M, Winqvist R. Mutation screening of Mre11 complex genes: indication of RAD50 involvement in breast and ovarian cancer susceptibility. J Med Genet 2003, 40:e131.
15. Heikkinen K, Rapakko K, Karppinen SM, Erkko H, Knuutila S, Lundan T, Mannermaa A, Borresen-Dale AL, Borg A, Barkardottir RB, Petrini J, Winqvist R. RAD50 and NBS1 are breast cancer susceptibility genes associated with genomic instability. Carcinogenesis 2006, 27:1593-1599.
16. Tommiska J, Seal S, Renwick A, Barfoot R, Baskcomb L, Jayatilake H, Bartkova J, Tallila J, Kaare M, Tamminen A, Heikkila P, Evans DG, Eccles D, Aittomaki K, Blomqvist C, Bartek J, Stratton MR, Nevanlinna H, Rahman N. Evaluation of RAD50 in familial breast cancer predisposition. Int J Cancer 2006, 118:2911-2916.
17. Wang X, Szabo C, Qian C, Amadio PG, Thibodeau SN, Cerhan JR, Petersen GM, Liu W, Couch FJ. Mutational analysis of thirty-two double-strand DNA break repair genes in breast and pancreatic cancers. Cancer Res 2008, 68:971-975.
18. Bartkova J, Tommiska J, Oplustilova L, Aaltonen K, Tamminen A, Heikkinen T, Mistrik M, Aittomaki K, Blomqvist C, Heikkila P, Lukas J, Nevanlinna H, Bartek J. Aberrations of the MRE11-RAD50-NBS1 DNA damage sensor complex in human breast cancer: MRE11 as a candidate familial cancer-predisposing gene. Mol Oncol 2008, 2:296-316.
19. Tavtigian SV, Oefner PJ, Babikyan D, Hartmann A, Healey S, Le Calvez-Kelm F, Lesueur F, Byrnes GB, Chuang SC, Forey N, Feuchtinger C, Gioia L, Hall J, Hashibe M, Herte B, McKay-Chopin S, Thomas A, Vallee MP, Voegele C, Webb PM, Whiteman DC, Sangrajrang S, Hopper JL, Southey MC, Andrulis IL, John EM, Chenevix-Trench G. Rare, evolutionarily unlikely missense substitutions in ATM confer increased risk of breast cancer. Am J Hum Genet 2009, 85:427-446.
20. Le Calvez-Kelm F, Lesueur F, Damiola F, Vallee M, Voegele C, Babikyan D, Durand G, Forey N, McKay-Chopin S, Robinot N, Nguyen-Dumont T, Thomas A, Byrnes GB, Hopper JL, Southey MC, Andrulis IL, John EM, Tavtigian SV. Rare, evolutionarily unlikely missense substitutions in CHEK2 contribute to breast cancer susceptibility: results from a breast cancer family registry case-control mutation-screening study. Breast Cancer Res 2011, 13:R6.
21. Park DJ, Lesueur F, Nguyen-Dumont T, Pertesi M, Odefrey F, Hammet F, Neuhausen SL, John EM, Andrulis IL, Terry MB, Daly M, Buys S, Le Calvez-Kelm F, Lonie A, Pope BJ, Tsimiklis H, Voegele C, Hilbers FM, Hoogerbrugge N, Barroso A, Osorio A, Giles GG, Devilee P, Benitez J, Hopper JL, Tavtigian SV, Goldgar DE, Southey MC. Rare mutations in XRCC2 increase the risk of breast cancer. Am J Hum Genet 2012, 90:734-739.
22. Le Calvez-Kelm F, Oliver J, Damiola F, Forey N, Robinot N, Durand G, Voegele C, Vallee MP, Byrnes G, Registry BC, Hopper JL, Southey MC, Andrulis IL, John EM, Tavtigian SV, Lesueur F. RAD51 and breast cancer susceptibility: no evidence for rare variant association in the Breast Cancer Family Registry Study. PLoS One 2012, 7:e52374.
23. John EM, Hopper JL, Beck JC, Knight JA, Neuhausen SL, Senie RT, Ziogas A, Andrulis IL, Anton-Culver H, Boyd N, Buys SS, Daly MB, O'Malley FP, Santella RM, Southey MC, Venne VL, Venter DJ, West DW, Whittemore AS, Seminara D. The Breast Cancer Family Registry: an infrastructure for cooperative multinational, interdisciplinary and translational studies of the genetic epidemiology of breast cancer. Breast Cancer Res 2004, 6:R375-R389.
24. Voegele C, Tavtigian SV, de Silva D, Cuber S, Thomas A, Le Calvez-Kelm F. A Laboratory Information Management System (LIMS) for a high throughput genetic platform aimed at candidate gene mutation screening. Bioinformatics 2007, 23:2504-2506.
25. Nguyen-Dumont T, Calvez-Kelm FL, Forey N, McKay-Chopin S, Garritano S, Gioia-Patricola L, De Silva D, Weigel R, Sangrajrang S, Lesueur F, Tavtigian SV. Description and validation of high-throughput simultaneous genotyping and mutation scanning by high-resolution melting curve analysis. Hum Mutat 2009, 30:884-890.
26. Garritano S, Gemignani F, Voegele C, Nguyen-Dumont T, Le Calvez-Kelm F, De Silva D, Lesueur F, Landi S, Tavtigian SV. Determining the effectiveness of High Resolution Melting analysis for SNP genotyping and mutation scanning at the TP53 locus. BMC Genet 2009, 10:5.
27. The exome variant server. [http://evs.gs.washington.edu/EVS/].
28. 1000 Genomes. [http://browser.1000genomes.org/index.html].
29. T-Coffee. [http://www.tcoffee.org/].
30. Wallace IM, O'Sullivan O, Higgins DG, Notredame C. M-Coffee: combining multiple sequence alignment methods with T-Coffee. Nucleic Acids Res 2006, 34:1692-1699.
31. Felsenstein J. PHYLIP - Phylogeny Inference Package (version 3.2). Cladistics 1989, 5:164-166.
32. Align GVGD. [http://agvgd.iarc.fr].
33. Tavtigian SV, Byrnes GB, Goldgar DE, Thomas A. Classification of rare missense substitutions, using risk surfaces, with genetic- and molecular-epidemiology applications. Hum Mutat 2008, 29:1342-1354.
34. Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 2009, 4:1073-1081.
35. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR. A method and server for predicting damaging missense mutations. Nat Methods 2010, 7:248-249.
36. Tavtigian SV, Greenblatt MS, Lesueur F, Byrnes GB. In silico analysis of missense substitutions using sequence-alignment based methods. Hum Mutat 2008, 29:1327-1336.
37. Yeo G, Burge CB. Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals. J Comput Biol 2004, 11:377-394.
38. Easton DF, Deffenbaugh AM, Pruss D, Frye C, Wenstrup RJ, Allen-Brady K, Tavtigian SV, Monteiro AN, Iversen ES, Couch FJ, Goldgar DE. A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes. Am J Hum Genet 2007, 81:873-883.
39. Vallee MP, Francy TC, Judkins MK, Babikyan D, Lesueur F, Gammon A, Goldgar DE, Couch FJ, Tavtigian SV. Classification of missense substitutions in the BRCA genes: a database dedicated to Ex-UVs. Hum Mutat 2012, 33:22-28.
40. NGRL 1000 Genomes Variant Access. [https://secure.ngrl.org.uk/1kg_querytool/].
41. Breast cancer information core. [http://research.nhgri.nih.gov/projects/bic/index.shtml].
42. van Puijenbroek M, van Asperen CJ, van Mil A, Devilee P, van Wezel T, Morreau H. Homozygosity for a CHEK2*1100delC mutation identified in familial colorectal cancer does not lead to a severe clinical phenotype. J Pathol 2005, 206:198-204.
43. Adank MA, Jonker MA, Kluijt I, van Mil SE, Oldenburg RA, Mooi WJ, Hogervorst FB, van den Ouweland AM, Gille JJ, Schmidt MK, van der Vaart AW, Meijers-Heijboer H, Waisfisz Q. CHEK2*1100delC homozygosity is associated with a high breast cancer risk in women. J Med Genet 2011, 48:860-863.
44. Huijts PE, Hollestelle A, Balliu B, Houwing-Duistermaat JJ, Meijers CM, Blom JC, Ozturk B, Krol-Warmerdam EM, Wijnen J, Berns EM, Martens JW, Seynaeve C, Kiemeney LA, van der Heijden HF, Tollenaar RA, Devilee P, van Asperen CJ. CHEK2*1100delC homozygosity in the Netherlands-prevalence and risk of breast and lung cancer. Eur J Hum Genet 2013, 22:46-51.
45. Bouwman P, van der Gulden H, van der Heijden I, Drost R, Klijn CN, Prasetyanti P, Pieterse M, Wientjens E, Seibler J, Hogervorst FB, Jonkers J. A high-throughput functional complementation assay for classification of BRCA1 missense variants. Cancer Discov 2013, 3:1142-1155.
46. Usui T, Ohta T, Oshiumi H, Tomizawa J, Ogawa H, Ogawa T. Complex formation and functional versatility of Mre11 of budding yeast in recombination. Cell 1998, 95:705-716.
47. InterPro protein sequence analysis and classification. [http://www.ebi.ac.uk/interpro/].
48. UniProt. [http://www.uniprot.org/].
49. NCBI conserved domains database. [http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml].
50. Marchler-Bauer A, Lu S, Anderson JB, Chitsaz F, Derbyshire MK, DeWeese-Scott C, Fong JH, Geer LY, Geer RC, Gonzales NR, Gwadz M, Hurwitz DI, Jackson JD, Ke Z, Lanczycki CJ, Lu F, Marchler GH, Mullokandov M, Omelchenko MV, Robertson CL, Song JS, Thanki N, Yamashita RA, Zhang D, Zhang N, Zheng C, Bryant SH. CDD: a Conserved Domain Database for the functional annotation of proteins. Nucleic Acids Res 2011, 39:D225-D229.
51. Schiller CB, Lammens K, Guerini I, Coordes B, Feldmann H, Schlauderer F, Mockel C, Schele A, Strasser K, Jackson SP, Hopfner KP. Structure of Mre11-Nbs1 complex yields insights into ataxia-telangiectasia-like disease mutations and DNA damage signaling. Nat Struct Mol Biol 2012, 19:693-700.
52. Hopfner KP, Karcher A, Craig L, Woo TT, Carney JP, Tainer JA. Structural biochemistry and interaction architecture of the DNA double-strand break repair Mre11 nuclease and Rad50-ATPase. Cell 2001, 105:473-485.
53. Williams RS, Moncalian G, Williams JS, Yamada Y, Limbo O, Shin DS, Groocock LM, Cahill D, Hitomi C, Guenther G, Moiani D, Carney JP, Russell P, Tainer JA. Mre11 dimers coordinate DNA end bridging and nuclease processing in double-strand-break repair. Cell 2008, 135:97-109.
54. Lammens K, Bemeleit DJ, Mockel C, Clausing E, Schele A, Hartung S, Schiller CB, Lucas M, Angermuller C, Soding J, Strasser K, Hopfner KP. The Mre11:Rad50 structure shows an ATP-dependent molecular clamp in DNA double-strand break repair. Cell 2011, 145:54-66.
55. Williams GJ, Williams RS, Williams JS, Moncalian G, Arvai AS, Limbo O, Guenther G, SilDas S, Hammel M, Russell P, Tainer JA. ABC ATPase signature helices in Rad50 link nucleotide state to Mre11 interface for DNA repair. Nat Struct Mol Biol 2011, 18:423-431.
56. Lim HS, Kim JS, Park YB, Gwon GH, Cho Y. Crystal structure of the Mre11-Rad50-ATPgammaS complex: understanding the interplay between Mre11 and Rad50. Genes Dev 2011, 25:1091-1104.
57. Dery U, Coulombe Y, Rodrigue A, Stasiak A, Richard S, Masson JY. A glycine-arginine domain in control of the human MRE11 DNA repair protein. Mol Cell Biol 2008, 28:3058-3069.
58. Boisvert FM, Dery U, Masson JY, Richard S. Arginine methylation of MRE11 by PRMT1 is required for DNA damage checkpoint control. Genes Dev 2005, 19:671-676.
59. Hopfner KP, Karcher A, Shin DS, Craig L, Arthur LM, Carney JP, Tainer JA. Structural biology of Rad50 ATPase: ATP-driven conformational control in DNA double-strand break repair and the ABC-ATPase superfamily. Cell 2000, 101:789-800.
60. Williams RS, Dodson GE, Limbo O, Yamada Y, Williams JS, Guenther G, Classen S, Glover JN, Iwasaki H, Russell P, Tainer JA. Nbs1 flexibly tethers Ctp1 and Mre11-Rad50 to coordinate DNA double-strand break processing and repair. Cell 2009, 139:87-99.
61. Lloyd J, Chapman JR, Clapperton JA, Haire LF, Hartsuiker E, Li J, Carr AM, Jackson SP, Smerdon SJ. A supramodular FHA/BRCT-repeat architecture mediates Nbs1 adaptor function in response to DNA damage. Cell 2009, 139:100-111.
62. Falck J, Coates J, Jackson SP. Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature 2005, 434:605-611.
63. You Z, Chahwan C, Bailis J, Hunter T, Russell P. ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1. Mol Cell Biol 2005, 25:5363-5379.
64. SIFT. [http://sift.jcvi.org/].
65. PolyPhen-2. [http://genetics.bwh.harvard.edu/pph2/].
66. di Masi A, Antoccia A. NBS1 heterozygosity and cancer risk. Curr Genomics 2008, 9:275-281.
67. di Masi A, Viganotti M, Polticelli F, Ascenzi P, Tanzarella C, Antoccia A. The R215W mutation in NBS1 impairs gamma-H2AX binding and affects DNA repair: molecular bases for the severe phenotype of 657del5/R215W Nijmegen breakage syndrome patients. Biochem Biophys Res Commun 2008, 369:835-840.
68. Dzikiewicz-Krawczyk A, Mosor M, Januszkiewicz D, Nowak J. Impact of heterozygous c.657-661del, p.I171V and p.R215W mutations in NBN on nibrin functions. Mutagenesis 2012, 27:337-343.
69. Delia D, Piane M, Buscemi G, Savio C, Palmeri S, Lulli P, Carlessi L, Fontanella E, Chessa L. MRE11 mutations and impaired ATM-dependent responses in an Italian family with ataxia-telangiectasia-like disorder. Hum Mol Genet 2004, 13:2155-2163.