Comprehensive annotation of splice junctions supports pervasive alternative splicing at the BRCA1 locus: A report from the ENIGMA consortium

Human Molecular Genetics

Volumn 23, Issue 14, 2014, Pages 3666-3680

  Colombo, Mara ^a   Blok, Marinus J ^b   Whiley, Phillip ^c,d   Santamariña, Marta ^e   Gutiérrez Enríquez, Sara ^f   Romero, Atocha ^g   Garre, Pilar ^g   Becker, Alexandra ^h,i   Smith, Lindsay Denise ^j   Vecchi, Giovanna De ^b   Brandão, Rita D ^b   Tserpelis, Demis ^b   Brown, Melissa ^d   Blanco, Ana ^a   Bonache, Sandra ^f   Menéndez, Mireia ^k   Houdayer, Claude ^l   Foglia, Claudia ^a   Fackenthal, James D ^m   Baralle, Diana ^j   Wappenschmidt, Barbara ^h,i   Díaz Rubio, Eduardo ^g   Caldés, Trinidad ^g   Walker, Logan ⁿ   Díez, Orland ^f,o   Vega, Ana ^e   Spurdle, Amanda B ^c   Radice, Paolo ^a   de la Hoya, Miguel ^g   more..

^a NATIONAL CANCER INSTITUTE   (Italy)

^b MAASTRICHT UNIVERSITY MEDICAL CENTER   (Netherlands)

^c QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

^d UNIVERSITY OF QUEENSLAND   (Australia)

^e UNIVERSITY OF SANTIAGO DE COMPOSTELA   (Spain)

^f UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^g HOSPITAL CLÍNICO SAN CARLOS   (Spain)

^h UNIVERSITY HOSPITAL OF COLOGNE   (Germany)

ⁱ UNIVERSITY OF COLOGNE   (Germany)

^j UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^k CATALAN INSTITUTE OF ONCOLOGY   (Spain)

^l INSTITUT CURIE   (France)

^m UNIVERSITY OF CHICAGO MEDICAL CENTER   (United States)

ⁿ UNIVERSITY OF OTAGO   (New Zealand)

^o HOSPITAL UNIVERSITARI VALL D HEBRON   (Spain)

more..

Author keywords

[No Author keywords available]

Indexed keywords

BRCA1 PROTEIN; RNA; ISOPROTEIN; MESSENGER RNA;

ALTERNATIVE RNA SPLICING; ARTICLE; BIOLOGICAL ACTIVITY; BLOOD ANALYSIS; BLOOD SAMPLING; BREAST; CELL JUNCTION; CONTROLLED STUDY; EXON; GENE CASSETTE; GENE EXPRESSION; GENE LOCUS; GENE SEQUENCE; HUMAN; HUMAN TISSUE; IN VITRO STUDY; MOLECULAR CLONING; MOLECULAR GENETICS; PRIORITY JOURNAL; PROTEIN ANALYSIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TUMOR SUPPRESSOR GENE; BLOOD; CLINICAL TRIAL; FEMALE; GENETICS; METABOLISM; MULTICENTER STUDY; SEQUENCE ANALYSIS;

ALTERNATIVE SPLICING; BRCA1 PROTEIN; BREAST; FEMALE; HUMANS; PROTEIN ISOFORMS; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; SEQUENCE ANALYSIS, RNA;

EID: 84902961280     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddu075     Document Type: Article

References (53)

1. Wang, E.T., Sandberg, R., Luo, S., Khrebtukova, I., Zhang, L., Mayr, C., Kingsmore, S.F., Schroth, G.P. and Burge, C.B. (2008) Alternative isoform regulation in human tissue transcriptomes. Nature, 456, 470-476.
2. Chen, M. and Manley, J.L. (2009) Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches. Nat. Rev. Mol. Cell Biol., 10, 741-754.
3. Djebali, S., Davis, C.A., Merkel, A., Dobin, A., Lassmann, T., Mortazavi, A., Tanzer, A., Lagarde, J., Lin, W., Schlesinger, F. et al. (2012) Landscape of transcription in human cells. Nature, 489, 101-108.
4. Mudge, J.M., Frankish, A., Fernandez-Banet, J., Alioto, T., Derrien, T., Howald, C., Reymond, A., Guigó , R., Hubbard, T. and Harrow, J. (2011) The origins, evolution, and functional potential of alternative splicing in vertebrates. Mol. Biol. Evol., 28, 2949-2959.
5. Blencowe, B.J. (2006) Alternative splicing: new insights from global analyses. Cell, 126, 37-47.
6. Kim, H., Klein, R., Majewski, J. and Ott, J. (2004) Estimating rates of alternative splicing in mammals and invertebrates. Nat. Genet., 36, 915-916.
7. Kim, E., Magen, A. and Ast, G. (2007) Different levels of alternative splicing among eukaryotes. Nucleic Acids Res., 35, 125-131.
8. Skandalis, A., Frampton, M., Seger, J. and Richards, M.H. (2010) The adaptive significance of unproductive alternative splicing in primates. RNA, 16, 2014-2022.
9. Tress, M.L., Martelli, P.L., Frankish, A., Reeves, G.A., Wesselink, J.J., Yeats, C., Olason, P.I., Albrecht, M., Hegyi, H., Giorgetti, A. et al. (2007) The implications of alternative splicing in the ENCODE protein complement. Proc. Natl. Acad. Sci. USA, 104, 5495-5500.
10. Frankish, A., Mudge, J.M., Thomas, M. and Harrow, J. (2012) The importance of identifying alternative splicing in vertebrate genome annotation. Database (Oxford), 2012, bas014.
11. Lewis, B.P., Green, R.E. and Brenner, S.E. (2003) Evidence for the widespread coupling of alternative splicing and nonsense-mediated mRNA decay in humans. Proc. Natl. Acad. Sci. USA, 100, 189-192.
12. Melamud, E. and Moult, J. (2009) Stochastic noise in splicing machinery. Nucl. Acids Res., 37, 4873-4886.
13. Miki, Y., Swensen, J., Shattuck-Eidens, D., Futreal, P.A., Harshman, K., Tavtigian, S., Liu, Q., Cochran, C., Bennett, L.M. and Ding, W. (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science, 266, 66-71.
14. Roy, R., Chun, J. and Powell, S.N. (2012) BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat. Rev. Cancer, 12, 68-78.
15. Walker, L.C., Whiley, P.J., Houdayer, C., Hansen, T.V.O., Vega, A., Santamarina, M., Blanco, A., Fachal, L., Southey, M.C., Lafferty, A. et al. (2013) Evaluation of a 5-tier scheme proposed for classification of sequence variants using bioinformatic and splicing assay data: inter-reviewer variability and promotion of minimum reporting guidelines. Hum. Mutat., 34, 1424-1431.
16. Orban, T.I. and Olah, E. (2003) Emerging roles of BRCA1 alternative splicing. Mol. Pathol., 56, 191-197.
17. Sevcik, J., Falk, M., Kleiblova, P., Lhota, F., Stefancikova, L., Janatova, M., Weiterova, L., Lukasova, E., Kozubek, S., Pohlreich, P. et al. (2012) The BRCA1 alternative splicing variant D14-15 with an in-frame deletion of part of the regulatory serine-containing domain (SCD) impairs the DNA repair capacity in MCF-7 cells. Cell Signal., 24, 1023-1030.
18. ElShamy, W.M. and Livingston, D.M. (2004) Identification of BRCA1-IRIS, a BRCA1 locus product. Nat. Cell Biol., 6, 954-967.
19. Fortin, J., Moisan, A.M., Dumont, M., Leblanc, G., Labrie, Y., Durocher, F., Bessette, P., Bridge, P., Chiquette, J., Laframboise, R. et al. (2005) A new alternative splice variant of BRCA1 containing an additional in-frame exon. Biochim. Biophys. Acta, 1731, 57-65.
20. Lixia, M., Zhijian, C., Chao, S., Chaojiang, G. and Congyi, Z. (2007) Alternative splicing of breast cancer associated gene BRCA1 from breast cancer cell line. J. Biochem. Mol. Biol., 40, 15-21.
21. Fetzer, S., Tworek, H.A., Piver, M.S. and Dicioccio, R.A. (1998) An alternative splice site junction in exon 1a of the BRCA1 gene. Cancer Genet. Cytogenet., 105, 90-92.
22. Gu, M., Li, H., Shen, C., Wu, L., Liu, W., Miao, L. and Zheng, C. (2010) Cloning and characterization of a new BRCA1 variant: a role for BRCT domains in apoptosis. Cancer Lett., 295, 205-213.
23. Xu, C.F., Brown, M.A., Chambers, J.A., Griffiths, B., Nicolai, H. and Solomon, E. (1995) Distinct transcription start sites generate two forms of BRCA1 mRNA. Hum. Mol. Genet., 4, 2259-2264.
24. Xu, C.F., Chambers, J.A., Nicolai, H., Brown, M.A., Hujeirat, Y., Mohammed, S., Hodgson, S., Kelsell, D.P., Spurr, N.K., Bishop, D.T. et al. (1997) Mutations and alternative splicing of the BRCA1 gene in UK breast/ovarian cancer families. Genes Chromosomes Cancer, 18, 102-110.
25. Claes, K., Vandesompele, J., Poppe, B., Dahan, K., Coene, I., De Paepe, A. and Messiaen, L. (2002) Pathological splice mutations outside the invariant AG/GTsplice sites of BRCA1 exon 5 increase alternative transcript levels in the 5′ end of the BRCA1 gene. Oncogene, 21, 4171-4175.
26. Dosil, V., Tosar, A., Cañadas, C., Pérez-Segura, P., Díaz-Rubio, E., Caldés, T. and de la Hoya, M. (2010) Alternative splicing and molecular characterization of splice site variants: BRCA1 c.591C.T as a case study. Clin. Chem., 56, 53-61.
27. Friedman, L.S., Szabo, C.I., Ostermeyer, E.A., Dowd, P., Butler, L., Park, T., Lee, M.K., Goode, E.L., Rowell, S.E. and King, M.C. (1995) Novel inherited mutations and variable expressivity of BRCA1 alleles, including the founder mutation 185delAG in Ashkenazi Jewish families. Am. J. Hum. Genet., 57, 1284-1297.
28. Tammaro, C., Raponi, M., Wilson, D.I. and Baralle,D. (2012) BRCA1 exon 11 alternative splicing, multiple functions and the association with cancer. Biochem. Soc. Trans., 40, 768-772.
29. Houdayer, C., Caux-Moncoutier, V., Krieger, S., Barrois, M., Bonnet, F., Bourdon, V., Bronner, M., Buisson, M., Coulet, F., Gaildrat, P. et al. (2012) Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants. Hum. Mutat., 33, 1228-1238.
30. Gowen, L.C., Johnson, B.L., Latour, A.M., Sulik, K.K. and Koller, B.H. (1996) Brca1 deficiency results in early embryonic lethality characterized by neuroepithelial abnormalities. Nat. Genet., 12, 191-194.
31. Hakem, R., de la Pompa, J.L., Sirard, C., Mo, R., Woo, M., Hakem, A., Wakeham, A., Potter, J., Reitmair, A., Billia, F. et al. (1996) The tumor suppressor gene Brca1 is required for embryonic cellular proliferation in the mouse. Cell, 85, 1009-1023.
32. Ludwig, T., Chapman, D.L., Papaioannou, V.E. and Efstratiadis, A. (1997) Targeted mutations of breast cancer susceptibility gene homologs in mice:lethal phenotypes of Brca1, Brca2, Brca1/Brca2, Brca1/p53, and Brca2/p53 nullizygous embryos. Genes Dev., 11, 1226-1241.
33. Hakem, R., de la Pompa, J.L., Elia, A., Potter, J. and Mak, T.W. (1997) Partial rescue of Brca1 (5-6) early embryonic lethality by p53 or p21 null mutation. Nat. Genet., 16, 298-302.
34. Shimizu, Y., Luk, H., Horio, D., Miron, P., Griswold, M., Iglehart, D., Hernandez, B., Killeen, J. and ElShamy, W.M. (2012) BRCA1-IRIS overexpression promotes formation of aggressive breast cancers. PLoS ONE, 7, e34102.
35. Claes, K., Poppe, B., Machackova, E., Coene, I., Foretova, L., De Paepe, A. and Messiaen, L. (2003) Differentiating pathogenic mutations from polymorphic alterations in the splice sites of BRCA1 and BRCA2. Genes Chromosomes Cancer, 37, 314-320.
36. Spurdle, A.B., Couch, F.J., Hogervorst, F.B.L., Radice, P. and Sinilnikova, O.M. and IARC Unclassified Genetic Variants Working Group. (2008) Prediction and assessment of splicing alterations: implications for clinical testing. Hum. Mutat., 29, 1304-1313.
37. Whiley, P., de la Hoya, M., Thomassen, M., Becker, A., Brandão, R., Pedersen, I.S., Montagna, M.,Menéndez, M., Quiles, F., Enríquez, S.G. et al. (2014) Comparison of mRNA splicing assay protocols across multiple laboratories: recommendations for best practice in standardized clinical testing. Clin. Chem., 60, 341-352.
38. Spurdle, A.B., Healey, S., Devereau, A., Hogervorst, F.B.L., Monteiro, A.N.A., Nathanson, K.L., Radice, P., Stoppa-Lyonnet, D., Tavtigian, S., Wappenschmidt, B. et al. (2012) ENIGMA - evidence-based network for the interpretation of germline mutant alleles: an international initiative to evaluate risk and clinical significance associated with sequence variation in BRCA1 and BRCA2 genes. Hum. Mutat., 33, 2-7.
39. Munnes, M., Zuther, I., Schmitz, B. and Doerfler, W. (2000) A Novel Insertional Mutation and Differentially Spliced mRNAs in the Human BRCA1 Gene. Gene Funct Dis, 1, 38-47.
40. Bonnet, C., Krieger, S., Vezain, M., Rousselin, A., Tournier, I., Martins, A., Berthet, P., Chevrier, A., Dugast, C., Layet, V. et al. (2008) 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., 45, 438-446.
41. Brandão, R.D., van Roozendaal, K., Tserpelis, D., Gómez García, E. and Blok, M.J. (2011) Characterisation of unclassified variants in the BRCA1/2 genes with a putative effect on splicing. Breast Cancer Res. Treat., 129, 971-982.
42. Pyne, M.T., Pruss, D., Ward, B.E. and Scholl, T. (1999) Acharacterization of genetic variants in BRCA1 intron 8 identifies a mutation and a polymorphism. Mutat. Res., 406, 101-107.
43. Hiller, M., Huse, K., Szafranski, K., Jahn, N., Hampe, J., Schreiber, S., Backofen, R. and Platzer, M. (2004) Widespread occurrence of alternative splicing at NAGNAG acceptors contributes to proteome plasticity. Nat. Genet., 36, 1255-1257.
44. De Garibay, G.R., Acedo, A., García-Casado, Z., Gutiérrez-Enríquez, S., Tosar, A., Romero, A., Garre, P., Llort, G., Thomassen, M., Díez, O. et al. (2014) Capillary electrophoresis analysis of conventional splicing assays:IARC analytical and clinical classification of 31 BRCA2 genetic variants. Hum. Mutat., 35, 53-57.
45. Mercer, T.R., Gerhardt, D.J., Dinger, M.E., Crawford, J., Trapnell, C., Jeddeloh, J.A., Mattick, J.S. and Rinn, J.L. (2012) Targeted RNA sequencing reveals the deep complexity of the human transcriptome. Nat. Biotechnol., 30, 99-104.
46. Buljan, M., Chalancon, G., Eustermann, S., Wagner, G.P., Fuxreiter, M., Bateman, A. and Babu, M.M. (2012) Tissue-specific splicing of disordered segments that embed binding motifs rewires protein interaction networks. Mol. Cell, 46, 871-883.
47. Cortese, M.S., Uversky, V.N. and Dunker, A.K. (2008) Intrinsic disorder in scaffold proteins: getting more from less. Prog. Biophys. Mol. Biol., 98, 85-106.
48. Uversky, V.N., Oldfield, C.J., Midic, U., Xie, H., Xue, B., Vucetic, S., Iakoucheva, L.M., Obradovic, Z. and Dunker, A.K. (2009) Unfoldomics of human diseases: linking protein intrinsic disorder with diseases. BMC Genomics, 10 (Suppl. 1), S7.
49. Kornblihtt, A.R., Schor, I.E., Alló , M., Dujardin, G., Petrillo, E. and Muñoz, M.J. (2013) Alternative splicing: a pivotal step between eukaryotic transcription and translation. Nat. Rev. Mol. Cell Biol., 14, 153-165.
50. Bouwman, P., van der Gulden, H., van der Heijden, I., Drost, R., Klijn, C.N., Prasetyanti, P., Pieterse, M., Wientjens, E., Seibler, J., Hogervorst, F.B. et al. (2013) A high-throughput functional complementation assay for classification of BRCA1 missense variants. Cancer Discov., 3, 42-55.
51. Sevcik, J., Falk, M., Macurek, L., Kleiblova, P., Lhota, F., Hojny, J., Stefancikova, L., Janatova, M., Bartek, J., Stribrna, J. et al. (2013) Expression of human BRCA1D17-19 alternative splicing variant with a truncated BRCT domain in MCF-7 cells results in impaired assembly of DNA repair complexes and aberrant DNA damage response. Cell Signal., 25, 1186-1193.
52. Szabo, C., Masiello, A., Ryan, J.F. and Brody, L.C. (2000) The breast cancer information core: database design, structure, and scope. Hum. Mutat., 16, 123-131.
53. Irimia, M., Rukov, J.L., Penny, D., Vinther, J., Garcia-Fernandez, J. and Roy, S.W. (2008) Origin of introns by 'intronization' of exonic sequences. Trends Genet., 24, 378-381.