Consequences of germline variation disrupting the constitutional translational initiation codon start sites of MLH1 and BRCA2: Use of potential alternative start sites and implications for predicting variant pathogenicity

Molecular Carcinogenesis

Volumn 54, Issue 7, 2015, Pages 513-522

  Parsons, Michael T ^a   Whiley, Phillip J ^a   Beesley, Jonathan ^a   Drost, Mark ^b   de Wind, Niels ^b   Thompson, Bryony A ^a,c   Marquart, Louise ^a   Hopper, John L ^d,e   Jenkins, Mark A ^d   Brown, Melissa A ^c   Tucker, Kathy ^f   Warwick, Linda ^g   Buchanan, Daniel D ^a   Spurdle, Amanda B ^a  

^a QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

^b LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^c UNIVERSITY OF QUEENSLAND   (Australia)

^d UNIVERSITY OF MELBOURNE   (Australia)

^e Seoul National University   (South Korea)

^f PRINCE OF WALES HOSPITAL   (Australia)

^g CANBERRA HOSPITAL   (Australia)

Author keywords

Cancer syndrome genes; In vitro assay; Unclassified variant

Indexed keywords

BRCA2 PROTEIN; NUCLEOTIDE; PROTEIN MLH1; BRCA2 PROTEIN, HUMAN; ISOPROTEIN; MLH1 PROTEIN, HUMAN; NUCLEAR PROTEIN; SIGNAL TRANSDUCING ADAPTOR PROTEIN; START CODON;

ADULT; ARTICLE; CANCER RISK; CARCINOGENICITY; CASE REPORT; CODON USAGE; EXON; FEMALE; GENE DELETION; GENETIC SCREENING; GENETIC VARIABILITY; GERMLINE MUTATION; HUMAN; IN VITRO STUDY; MALE; MIDDLE AGED; MISMATCH REPAIR; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN FUNCTION; START CODON; TRANSLATION INITIATION; ALTERNATIVE RNA SPLICING; GENETICS; NEOPLASM; PROTEIN SYNTHESIS; TUMOR SUPPRESSOR GENE;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ALTERNATIVE SPLICING; BRCA2 PROTEIN; CODON, INITIATOR; DNA MISMATCH REPAIR; EXONS; GENES, BRCA2; HUMANS; NEOPLASMS; NUCLEAR PROTEINS; PROTEIN BIOSYNTHESIS; PROTEIN ISOFORMS;

EID: 84930766350     PISSN: 08991987     EISSN: 10982744     Source Type: Journal    
DOI: 10.1002/mc.22116     Document Type: Article

References (38)

1. Parsons MT, Buchanan DD, Thompson B, Young JP, Spurdle AB. Correlation of tumour BRAF mutations and MLH1 methylation with germline mismatch repair (MMR) gene mutation status: A literature review assessing utility of tumour features for MMR variant classification. J Med Genet 2012; 49:151-157.
2. Thompson BA, Goldgar DE, Paterson C, et al. A multifactorial likelihood model for MMR gene variant classification incorporating probabilities based on sequence bioinformatics and tumor characteristics: A report from the Colon Cancer Family Registry. Hum Mutat 2013; 34:200-209.
3. Thompson BA, Greenblatt MS, Vallee MP, et al. Calibration of multiple in silico tools for predicting pathogenicity of mismatch repair gene missense substitutions. Hum Mutat 2013; 34:255-265.
4. Goldgar DE, Easton DF, Byrnes GB, Spurdle AB, Iversen ES, Greenblatt MS. Genetic evidence and integration of various data sources for classifying uncertain variants into a single model. Hum Mutat 2008; 29:1265-1272.
5. Plon SE, Eccles DM, Easton D, et al. Sequence variant classification and reporting: Recommendations for improving the interpretation of cancer susceptibility genetic test results. Hum Mutat 2008; 29:1282-1291.
6. Spurdle AB. Clinical relevance of rare germline sequence variants in cancer genes: Evolution and application of classification models. Curr Opin Genet Dev 2010; 20:315-323.
7. Drost M, Zonneveld JB, van Dijk L, et al. A cell-free assay for the functional analysis of variants of the mismatch repair protein MLH1. Hum Mutat 2010; 31:247-253.
8. Farrugia DJ, Agarwal MK, Pankratz VS, et al. Functional assays for classification of BRCA2 variants of uncertain significance. Cancer Res 2008; 68:3523-3531.
9. Millot GA, Carvalho MA, Caputo SM, et al. A guide for functional analysis of BRCA1 variants of uncertain significance. Hum Mutat 2012; 33:1526-1537.
10. Raevaara TE, Korhonen MK, Lohi H, et al. Functional significance and clinical phenotype of nontruncating mismatch repair variants of MLH1. Gastroenterology 2005; 129:537-549.
11. Spurdle AB, Couch FJ, Hogervorst FB, Radice P, Sinilnikova OM. Prediction and assessment of splicing alterations: Implications for clinical testing. Hum Mutat 2008; 29:1304-1313.
12. Houdayer C, Caux-Moncoutier V, Krieger S, et al. 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 2012; 33:1228-1238.
13. Brewster BL, Rossiello F, French JD, et al. Identification of fifteen novel germline variants in the BRCA1 3′UTR reveals a variant in a breast cancer case that introduces a functional miR-103 target site. Hum Mutat 2012; 33:1665-1675.
14. Nicoloso MS, Sun H, Spizzo R, et al. Single-nucleotide polymorphisms inside microRNA target sites influence tumor susceptibility. Cancer Res 2010; 70:2789-2798.
15. Pamula J, Krzesniak M, Zientek H, Pekala W, Rusin M, Grzybowska E. Functional impact of sequence alterations found in BRCA1 promoter/5′UTR region in breast/ovarian cancer families from Upper Silesia, Poland. Hered Cancer Clin Pract 2006; 4:20-24.
16. Liu J, Prolla G, Rostagno A, Chiarle R, Feiner H, Inghirami G. Initiation of translation from a downstream in-frame AUG codon on BRCA1 can generate the novel isoform protein DeltaBRCA1(17aa). Oncogene 2000; 19:2767-2773.
17. Wang XQ, Rothnagel JA. 5′-Untranslated regions with multiple upstream AUG codons can support low-level translation via leaky scanning and reinitiation. Nucleic Acids Res 2004; 32:1382-1391.
18. Kochetov AV. Alternative translation start sites and hidden coding potential of eukaryotic mRNAs. Bioessays 2008; 30:683-691.
19. Lukowski SW, Bombieri C, Trezise AE. Disrupted post-transcriptional regulation of the cystic fibrosis transmembrane conductance regulator (CFTR) by a 5′UTR mutation is associated with a CFTR-related disease. Hum Mutat 2011; 32:E2266-E2282.
20. Thomassen M, Blanco A, Montagna M, et al. Characterization of BRCA1 and BRCA2 splicing variants: A collaborative report by ENIGMA consortium members. Breast Cancer Res Treat 2012; 132:1009-1023.
21. Kets CM, Hoogerbrugge N, van Krieken JH, Goossens M, Brunner HG, Ligtenberg MJ. Compound heterozygosity for two MSH2 mutations suggests mild consequences of the initiation codon variant c.1A>G of MSH2. Eur J Hum Genet 2009; 17:159-164.
22. Cyr JL, Brown GD, Stroop J, Heinen CD. The predicted truncation from a cancer-associated variant of the MSH2 initiation codon alters activity of the MSH2-MSH6 mismatch repair complex. Mol Carcinog 2012; 51:647-658.
23. Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology 1999; 116:1453-1456.
24. Winship I, Win AK. The Australasian Colorectal Cancer Family Registry. Med J Aust 2012; 197:480-481.
25. Desmet FO, Hamroun D, Lalande M, Collod-Beroud G, Claustres M, Beroud C. Human splicing finder: An online bioinformatics tool to predict splicing signals. Nucleic Acids Res 2009; 37:e67.
26. Ban C, Junop M, Yang W. Transformation of MutL by ATP binding and hydrolysis: A switch in DNA mismatch repair. Cell 1999; 97:85-97.
27. Senapathy P. Origin of eukaryotic introns: A hypothesis, based on codon distribution statistics in genes, and its implications. Proc Natl Acad Sci USA 1986; 83:2133-2137.
28. Senapathy P, Shapiro MB, Harris NL. Splice junctions, branch point sites, and exons: Sequence statistics, identification, and applications to genome project. Methods Enzymol 1990; 183:252-278.
29. Stover ML, Primorac D, Liu SC, McKinstry MB, Rowe DW. Defective splicing of mRNA from one COL1A1 allele of type I collagen in nondeforming (type I) osteogenesis imperfecta. J Clin Invest 1993; 92:1994-2002.
30. Wang XQ, Hadwen T, Rothnagel JA. Green fluorescent protein as a reporter in translational assays. Anal Biochem 2005; 336:135-137.
31. Wang XQ, Rothnagel JA. Post-transcriptional regulation of the gli1 oncogene by the expression of alternative 5′ untranslated regions. J Biol Chem 2001; 276:1311-1316.
32. Waldo GS, Standish BM, Berendzen J, Terwilliger TC. Rapid protein-folding assay using green fluorescent protein. Nat Biotechnol 1999; 17:691-695.
33. Bouwman P, van der Gulden H, van der Heijden I, et al. A high-throughput functional complementation assay for classification of BRCA1 missense variants. Cancer Discov 2013; 3:1142-1155.
34. Kuznetsov SG, Liu P, Sharan SK. Mouse embryonic stem cell-based functional assay to evaluate mutations in BRCA2. Nat Med 2008; 14:875-881.
35. Hinrichsen I, Brieger A, Trojan J, Zeuzem S, Nilbert M, Plotz G. Expression defect size among unclassified MLH1 variants determines pathogenicity in Lynch syndrome diagnosis. Clin Cancer Res 2013; 19:2432-2441.
36. Iversen ES Jr, Couch FJ, Goldgar DE, Tavtigian SV, Monteiro AN. A computational method to classify variants of uncertain significance using functional assay data with application to BRCA1. Cancer Epidemiol Biomarkers Prev 2011; 20:1078-1088.
37. Rasmussen LJ, Heinen CD, Royer-Pokora B, et al. Pathological assessment of mismatch repair gene variants in lynch syndrome: Past, present and future. Hum Mutat 2012; 33:1617-1625.
38. Heinen CD, Juel Rasmussen L. Determining the functional significance of mismatch repair gene missense variants using biochemical and cellular assays. Hered Cancer Clin Pract 2012; 10:9.