Multiple sequence variants of BRCA2 exon 7 alter splicing regulation

Journal of Medical Genetics

Volumn 49, Issue 10, 2012, Pages 609-617

  Gaildrat, Pascaline ^a,b,c   Krieger, Sophie ^a,d,e   Di Giacomo, Daniela ^a,b   Abdat, Julie ^a   Révillion, Françoise ^f   Caputo, Sandrine ^g   Vaur, Dominique ^a,d   Jamard, Estelle ^d   Bohers, Elodie ^a   Ledemeney, Danielle ^d   Peyrat, Jean Philippe ^f   Houdayer, Claude ^h   Rouleau, Etienne ^g   Lidereau, Rosette ^g   Frébourg, Thierry ^a,b,c   Hardouin, Agnès ^a,d   Tosi, Mario ^a,b   Martins, Alexandra ^a,b  

^a INSERM   (France)

^b UNIVERSITY OF ROUEN   (France)

^c ROUEN UNIVERSITY HOSPITAL   (France)

^d CENTRE FRANÇOIS BACLESSE   (France)

^e UNIVERSITÉ DE CAEN   (France)

^f CENTRE OSCAR LAMBRET   (France)

^g INSTITUT CURIE   (France)

^h UNIVERSITÉ PARIS DESCARTES   (France)

Author keywords

[No Author keywords available]

Indexed keywords

BRCA2 PROTEIN;

ARTICLE; CONTROLLED STUDY; DATA BASE; DNA SPLICING; EXON; GENE MUTATION; GENOTYPING TECHNIQUE; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PYROSEQUENCING; QUANTITATIVE ASSAY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; WILD TYPE;

ALLELES; ALTERNATIVE SPLICING; BASE SEQUENCE; CELL LINE, TUMOR; COMPUTATIONAL BIOLOGY; DATABASES, NUCLEIC ACID; ENHANCER ELEMENTS, GENETIC; EXONS; FRANCE; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE ORDER; GENE SILENCING; GENES, BRCA2; GENETIC VARIATION; HUMANS; MOLECULAR SEQUENCE DATA; MUTATION; RNA; RNA SPLICE SITES;

EID: 84870293904     PISSN: 00222593     EISSN: 14686244     Source Type: Journal    
DOI: 10.1136/jmedgenet-2012-100965     Document Type: Article

References (34)

1. 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;81:873-83.
2. Caputo S, Benboudjema L, Sinilnikova O, Rouleau E, Béroud C, Lidereau R, the French BRCA GGC Consortium. Description and analysis of genetic variants in French hereditary breast and ovarian cancer families recorded in the UMD-BRCA1/BRCA2 databases. Nucleic Acids Res 2012;40:992-1002.
3. Goldgar DE, Easton DF, Byrnes GB, Spurdle AB, Iversen ES, Greenblatt MS, IARC Unclassified Genetic Variants Working Group. Genetic evidence and integration of various data sources for classifying uncertain variants into a single model. Hum Mutat 2008;29:1265-72.
4. Spurdle AB, Lakhani SR, Da Silva LM, Balleine RL, Goldgar DE, kConFab Investigators. Bayes analysis provides evidence of pathogenicity for the BRCA1 c.135-1G>T (IVS3-1) and BRCA2 c.7977-1G>C (IVS17-1) variants displaying in vitro splicing results of equivocal clinical significance. Hum Mutat 2010;31:E1141-5.
5. Lindor NM, Guidugli L, Wang X, Vallée MP, Monteiro AN, Tavtigian S, Goldgar DE, Couch FJ. A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS). Hum Mutat 2012;33:8-21.
6. Walker LC, Whiley PJ, Couch FJ, Farrugia DJ, Healey S, Eccles DM, Lin F, Butler SA, Goff SA, Thompson BA, Lakhani SR, Da Silva LM, Tavtigian SV, Goldgar DE, Brown MA, Spurdle AB, kConFab Investigators. Detection of splicing aberrations caused by BRCA1 and BRCA2 sequence variants encoding missense substitutions: implications for prediction of pathogenicity. Hum Mutat 2010;31:E1484-505.
7. Whiley PJ, Guidugli L, Walker LC, Healey S, Thompson BA, Lakhani SR, Da Silva LM, Tavtigian SV, Goldgar DE, Brown MA, Couch FJ, Spurdle AB, kConFab Investigators. Splicing and multifactorial analysis of intronic BRCA1 and BRCA2 sequence variants identifies clinically significant splicing aberrations up to 12 nucleotides from the intron/exon boundary. Hum Mutat 2011;32:678-87.
8. Vallée 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;33:22-8.
9. Cartegni L, Chew SL, Krainer AR. Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nat Rev Genet 2002;3:285-98.
10. Baralle D, Baralle M. Splicing in action: assessing disease causing sequence changes. J Med Genet 2005;42:737-48.
11. Spurdle AB, Couch FJ, Hogervorst FB, Radice P, Sinilnikova OM, IARC Unclassified Genetic Variants Working Group. Prediction and assessment of splicing alterations: implications for clinical testing. Hum Mutat 2008;29:1304-13.
12. Cooper TA, Wan L, Dreyfuss G. RNA and disease. Cell 2009;136:777-93.
13. Buratti E, Baralle FE. Influence of RNA secondary structure on the pre-mRNA splicing process. Mol Cell Biol 2004;24:10505-14.
14. Ke S, Shang S, Kalachikov SM, Morozova I, Yu L, Russo JJ, Ju J, Chasin LA. Quantitative evaluation of all hexamers as exonic splicing elements. Genome Res 2011;21:1360-74.
15. Lim KH, Ferraris L, Filloux ME, Raphael BJ, Fairbrother WG. Using positional distribution to identify splicing elements and predict pre-mRNA processing defects in human genes. Proc Natl Acad Sci USA 2011;108:11093-8.
16. Théry JC, Krieger S, Gaildrat P, Révillion F, Buisine MP, Killian A, Duponchel C, Rousselin A, Vaur D, Peyrat JP, Berthet P, Frébourg T, Martins A, Hardouin A, Tosi M. Contribution of bioinformatics predictions and functional splicing assays to the interpretation of unclassified variants of the BRCA genes. Eur J Hum Genet 2011;19:1052-8.
17. Gaffney EV. A cell line (HBL-100) established from human breast milk. Cell Tissue Res 1982;227:563-8.
18. Soule HD, Vazguez J, Long A, Albert S, Brennan M. A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst 1973;51:1409-16.
19. Tournier I, Vezain M, Martins A, Charbonnier F, Baert-Desurmont S, Olschwang S, Wang Q, Buisine MP, Soret J, Tazi J, Frébourg T, Tosi M. A large fraction of unclassified variants of the mismatch repair genes MLH1 and MSH2 is associated with splicing defects. Hum Mutat 2008;29:1412-24.
20. Bonnet C, Krieger S, Vezain M, Rousselin A, Tournier I, Martins A, Berthet P, Chevrier A, Dugast C, Layet V, Rossi A, Lidereau R, Frébourg T, Hardouin A, Tosi M. Screening BRCA1 and BRCA2 unclassified variants for splicing mutations using reverse transcription PCR on patient RNA and an ex vivo assay based on a splicing reporter minigene. J Med Genet 2008;45:438-46.
21. Gaildrat P, Killian A, Martins A, Tournier I, Frébourg T, Tosi M. Use of splicing reporter minigene assay to evaluate the effect on splicing of unclassified genetic variants. Methods Mol Biol 2010;653:249-57.
22. Gaildrat P, Krieger S, Thery JC, Killian A, Rousselin A, Berthet P, Frebourg T, Hardouin A, Martins A, Tosi M. The BRCA1 c.5434C>G (p.Pro1812Ala) variant induces a deleterious exon 23 skipping by affecting exonic splicing regulatory elements. J Med Genet 2010;47:398-403.
23. Colombo M, Ripamonti CB, Pensotti V, Foglia C, Peissel B, Pierotti MA, Manoukian S, Radice P. An unusual BRCA2 allele carrying two splice site mutations. Ann Oncol 2009;20:1143-4.
24. Pensabene M, Spagnoletti I, Capuano I, Condello C, Pepe S, Contegiacomo A, Lombardi G, Bevilacqua G, Caligo MA. Two mutations of BRCA2 gene at exon and splicing site in a woman who underwent oncogenetic counseling. Ann Oncol 2009;20:874-8.
25. Houdayer C, Dehainault C, Mattler C, Michaux D, Caux-Moncoutier V, Pagès-Berhouet S, d'Enghien CD, Laugé A, Castera L, Gauthier-Villars M, Stoppa-Lyonnet D. Evaluation of in silico splice tools for decision-making in molecular diagnosis. Hum Mutat 2008;29:975-82.
26. Sanz DJ, Acedo A, Infante M, Durán M, Pérez-Cabornero L, Esteban-Cardeñosa E, Lastra E, Pagani F, Miner C, Velasco EA. A high proportion of DNA variants of BRCA1 and BRCA2 is associated with aberrant splicing in breast/ovarian cancer patients. Clin Cancer Res 2010;16:1957-67.
27. Biswas K, Das R, Alter BP, Kuznetsov SG, Stauffer S, North SL, Burkett S, Brody LC, Meyer S, Byrd RA, Sharan SK. A comprehensive functional characterization of BRCA2 variants associated with Fanconi anemia using mouse ES cell-based assay. Blood 2011;118:2430-42.
28. Fackenthal JD, Cartegni L, Krainer AR, Olopade OI. BRCA2 T2722R is a deleterious allele that causes exon skipping. Am J Hum Genet 2002;71:625-31.
29. Pagani F, Stuani C, Tzetis M, Kanavakis E, Efthymiadou A, Doudounakis S, Casals T, Baralle FE. New type of disease causing mutations: the example of the composite exonic regulatory elements of splicing in CFTR exon 12. Hum Mol Genet 2003;12:1111-20.
30. Sterne-Weiler T, Howard J, Mort M, Cooper DN, Sanford JR. Loss of exon identity is a common mechanism of human inherited disease. Genome Res 2011;21:1563-71.
31. Pagani F, Raponi M, Baralle FE. Synonymous mutations in CFTR exon 12 affect splicing and are not neutral in evolution. Proc Natl Acad Sci USA 2005;102:6368-72.
32. Plon SE, Eccles DM, Easton D, Foulkes WD, Genuardi M, Greenblatt MS, Hogervorst FB, Hoogerbrugge N, Spurdle AB, Tavtigian SV, IARC Unclassified Genetic Variants Working Group. Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results. Hum Mutat 2008;29:1282-91.
33. Tavtigian SV, Greenblatt MS, Goldgar DE, Boffetta P, IARC Unclassified Genetic Variants Working Group. Assessing pathogenicity: overview of results from the IARC Unclassified Genetic Variants Working Group. Hum Mutat 2008;29:1261-4.
34. Alimonti A, Carracedo A, Clohessy JG, Trotman LC, Nardella C, Egia A, Salmena L, Sampieri K, Haveman WJ, Brogi E, Richardson AL, Zhang J, Pandolfi PP. Subtle variations in Pten dose determine cancer susceptibility. Nat Genet 2010;42:454-8.