Integrated analysis of unclassified variants in mismatch repair genes

Genetics in Medicine

Volumn 13, Issue 2, 2011, Pages 115-124

  Pastrello, Chiara ^a   Pin, Elisa ^a   Marroni, Fabio ^b   Bedin, Chiara ^c   Fornasarig, Mara ^a   Tibiletti, Maria Grazia ^d   Oliani, Cristina ^e   De Leon, Maurizio Ponz ^f   Urso, Emanuele Damiano ^c   Puppa, Lara Della ^a   Agostini, Marco ^c   Viel, Alessandra ^a  

^a CENTRO DI RIFERIMENTO ONCOLOGICO   (Italy)

^b Institute of Applied Genomics   (Italy)

^c UNIVERSITY OF PADOVA   (Italy)

^d UNIVERSITY OF INSUBRIA   (Italy)

^e Montecchio Hospital   (Italy)

^f UNIVERSITY OF MODENA AND REGGIO EMILIA   (Italy)

Author keywords

colorectal cancer; Lynch syndrome; mismatch repair; multifactorial likelihood; unclassified variant

Indexed keywords

MISMATCH REPAIR PROTEIN PMS2; PROTEIN MLH1; PROTEIN MSH2; PROTEIN MSH6;

ARTICLE; CONTROLLED STUDY; DISEASE ASSOCIATION; GENE MUTATION; GENETIC ANALYSIS; GENETIC SCREENING; GENETIC VARIABILITY; HEREDITARY NONPOLYPOSIS COLORECTAL CANCER; HUMAN; MAJOR CLINICAL STUDY; MISMATCH REPAIR; MISSENSE MUTATION; MUTATIONAL ANALYSIS; PATHOGENESIS; PATHOGENICITY;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ADENOSINE TRIPHOSPHATASES; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; COLORECTAL NEOPLASMS, HEREDITARY NONPOLYPOSIS; DATA INTERPRETATION, STATISTICAL; DNA MISMATCH REPAIR; DNA REPAIR ENZYMES; DNA-BINDING PROTEINS; GENETIC PREDISPOSITION TO DISEASE; GENETIC VARIATION; HETEROZYGOTE; HUMANS; LOSS OF HETEROZYGOSITY; MICROSATELLITE INSTABILITY; MUTATION; MUTS HOMOLOG 2 PROTEIN; NUCLEAR PROTEINS;

EID: 79951575821     PISSN: 10983600     EISSN: None     Source Type: Journal    
DOI: 10.1097/GIM.0b013e3182011489     Document Type: Article

References (42)

1. Lynch HT, Lynch PM, Lanspa SJ, Snyder CL, Lynch JF, Boland CR. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet 2009;76: 1-18.
2. Genuardi M, Carrara S, Anti M, Ponz de Leòn M, Viel A. Assessment of pathogenicity criteria for constitutional missense mutations of the hereditary nonpolyposis colorectal cancer genes MLH1 and MSH2. Eur J Hum Genet 1999;7:778-782. (Pubitemid 29516236)
3. Tavtigian SV, Greenblatt MS, Goldgar DE, Boffetta P. Assessing pathoge-nicity: overview of results from the IARC Unclassified Genetic Variants Working Group. Hum Mutat 2008;29:1261-1264.
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. Greenblatt MS, Brody LC, Foulkes WD, et al. Locus-specific databases and recommendations to strengthen their contribution to the classification of variants in cancer susceptibility genes. Hum Mutat 2008;29:1273-1281.
6. 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.
7. Hofstra RM, Spurdle AB, Eccles D, et al. Tumor characteristics as an analytic tool for classifying genetic variants of uncertain clinical significance. Hum Mutat 2008;29:1292-1303.
8. 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.
9. Couch FJ, Rasmussen LJ, Hofstra R, Monteiro AN, Greenblatt MS, de Wind N. Assessment of functional effects of unclassified genetic variants. Hum Mutat 2008;29:1314-1326.
10. Tavtigian SV, Greenblatt MS, Lesueur F, Byrnes GB. In silico analysis of missense substitutions using sequence-alignment based methods. Hum Mu-tat 2008;29:1327-1336.
11. Ou J, Niessen RC, Vonk J, Westers H, Hofstra RM, Sijmons RH. A database to support the interpretation of human mismatch repair gene variants. Hum Mutat 2008;29:1337-1341.
12. 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.
13. Goldgar DE, Easton DF, Deffenbaugh AM, et al. Integrated evaluation of DNA sequence variants of unknown clinical significance: application to BRCA1 and BRCA2. Am J Hum Genet 2004;75:535-544. (Pubitemid 39244769)
14. Baudhuin LM, Burgart LJ, Leontovich O, Thibodeau SN. Use of microsat-ellite instability and immunohistochemistry testing for the identification of individuals at risk for Lynch syndrome. Fam Cancer 2005;4:255-265. (Pubitemid 41242196)
15. Laghi L, Bianchi P, Malesci A. Differences and evolution of the methods for the assessment of microsatellite instability. Oncogene 2008;27:6313-6321.
16. Shimodaira H, Filosi N, Shibata H, et al. Functional analysis of human MLH1 mutations in Saccharomyces cerevisiae. Nat Genet 1998;19:384-389. (Pubitemid 28357913)
17. Kondo E, Suzuki H, Horii A, Fukushige S. A yeast two-hybrid assay provides a simple way to evaluate the vast majority of hMLH1 germ-line mutations. Cancer Res 2003;63:3302-3308. (Pubitemid 36735887)
18. 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. (Pubitemid 41096642)
19. Takahashi M, Shimodaira H, Andreutti-Zaugg C, Iggo R, Kolodner RD, Ishioka C. Functional analysis of human MLH1 variants using yeast and in vitro mismatch repair assays. Cancer Res 2007;67:4595-4604. (Pubitemid 46910164)
20. Perera S, Bapat B. The MLH1 variants p.Arg265Cys and p.Lys618Ala affect protein stability while p.Leu749Gln affects heterodimer formation. Hum Mutat 2008;29:332.
21. 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.
22. Ollila S, Dermadi Bebek D, Jiricny J, Nyström M. Mechanisms of patho-genicity in human MSH2 missense mutants. Hum Mutat 2008;29:1355-1363.
23. Trojan J, Zeuzem S, Randolph A, et al. Functional analysis of hMLH1 variants and HNPCC-related mutations using a human expression system. Gastroenterology 2002;122:211-219. (Pubitemid 34049209)
24. Arnold S, Buchanan DD, Barker M, et al. Classifying MLH1 and MSH2 variants using bioinformatic prediction, splicing assays, segregation, and tumor characteristics. Hum Mutat 2009;30:757-770.
25. Sweeting MJ, Sutton AJ, Lambert PC. What to add to nothing? Use and avoidance of continuity corrections in meta-analysis of sparse data. Stat Med 2004;23:1351-1375. (Pubitemid 38594143)
26. Karchin R, Agarwal M, Sali A, Couch F, Beattie MS. Classifying variants of undetermined significance in BRCA2 with protein likelihood ratios. Cancer Inform 2008;6:203-216.
27. Lastella P, Surdo NC, Resta N, Guanti G, Stella A. In silico and in vivo splicing analysis of MLH1 and MSH2 missense mutations shows exon- and tissue-specific effects. BMC Genomics 2006;7:243.
28. Engel C, Forberg J, Holinski-Feder E, et al. Novel strategy for optimal sequential application of clinical criteria, immunohistochemistry and micro-satellite analysis in the diagnosis of hereditary nonpolyposis colorectal cancer. Int J Cancer 2006;118:115-122. (Pubitemid 41681587)
29. Easton DF, Deffenbaugh AM, Pruss D, et al. 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. (Pubitemid 47580242)
30. Thompson D, Easton DF, Goldgar DE. A full-likelihood method for the evaluation of causality of sequence variants from family data. Am J Hum Genet 2003;73:652-655. (Pubitemid 37076278)
31. Marroni F, Pastrello C, Benatti P et al. A genetic model for determining MSH2 and MLH1 carrier probabilities based on family history and tumor microsatellite instability. Clin Genet 2006;69:254-262. (Pubitemid 43349009)
32. Viel A, Novella E, Genuardi M, et al. Lack of PMS2 gene-truncating mutations in patients with hereditary colorectal cancer. Int J Oncol 1998; 13:565-569. (Pubitemid 28372682)
33. Agostini M, Tibiletti MG, Lucci-Cordisco E, et al. Two PMS2 mutations in a Turcot syndrome family with small bowel cancers. Am J Gastroenterol 2005;100:1886-1891. (Pubitemid 41648446)
34. Barnetson RA, Cartwright N, van Vliet A, et al. Classification of ambiguous mutations in DNA mismatch repair genes identified in a population-based study of colorectal cancer. Hum Mutat 2008;29:367-374. (Pubitemid 351364938)
35. Ollila S, Sarantaus L, Kariola R, et al. Pathogenicity of MSH2 missense mutations is typically associated with impaired repair capability of the mutated protein. Gastroenterology 2006;131:1408-1417. (Pubitemid 44708945)
36. Gammie AE, Erdeniz N, Beaver J, Devlin B, Nanji A, Rose MD. Functional characterization of pathogenic human MSH2 missense mutations in Saccha-romyces cerevisiae. Genetics 2007;177:707-721. (Pubitemid 350005626)
37. Nakagawa H, Lockman JC, Frankel WL, et al. Mismatch repair gene PMS2: disease causing germline mutations are frequent in patients whose tumors stain negative for PMS2 protein, but paralogous genes obscure mutation detection and interpretation. Cancer Res 2004;64:4721-4727. (Pubitemid 38924513)
38. Lagerstedt Robinson K, Liu T, Vandrovcova J, et al. Lynch syndrome (hereditary nonpolyposis colorectal cancer) diagnostics. J Natl Cancer Inst 2007;99:291-299. (Pubitemid 47073492)
39. Genuardi M, Viel A, Bonora D, et al. Characterization of MLH1 and MSH2 alternative splicing and its relevance to molecular testing of colorectal cancer susceptibility. Hum Genet 1998;102:15-20. (Pubitemid 28185256)
40. Lastella P, Resta N, Miccolis I, Quagliarella A, Guanti G, Stella A. Site directed mutagenesis of hMLH1 exonic splicing enhancers does not correlate with splicing disruption. J Med Genet 2004;41:e72.
41. Auclair J, Busine MP, Navarro C, et al. Systematic mRNA analysis for the effect of MLH1 and MSH2 missense and silent mutations on aberrant splicing. Hum Mutat 2006;27:145-154. (Pubitemid 43238030)
42. 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.