Boland CR, Lynch HT (2013) The history of Lynch syndrome. Fam Cancer 12:145–157
Article PubMed PubMed Central Google Scholar
Win AK, Jenkins MA, Dowty JG, Antoniou AC, Lee A, Giles GG, Buchanan DD, Clendenning M, Rosty C, Ahnen DJ, Thibodeau SN, Casey G, Gallinger S, Le Marchand L, Haile RW, Potter JD, Zheng Y, Lindor NM, Newcomb PA, Hopper JL, MacInnis RJ (2017) Prevalence and penetrance of major genes and polygenes for colorectal Cancer. Cancer Epidemiol Biomarkers Prev 26:404–412
Article CAS PubMed Google Scholar
Lynch HT, Snyder CL, Shaw TG, Heinen CD, Hitchins MP (2015) Milestones of Lynch syndrome: 1895–2015. Nat Rev Cancer 15:181–194
Article CAS PubMed Google Scholar
Møller P, Seppälä TT, Bernstein I, Holinski-Feder E, Sala P, Gareth Evans D, Lindblom A, Macrae F, Blanco I, Sijmons RH, Jeffries J, Vasen HFA, Burn J, Nakken S, Hovig E, Rødland EA, Tharmaratnam K, de Vos Tot Nederveen Cappel WH, Hill J, Wijnen JT, Jenkins MA, Green K, Lalloo F, Sunde L, Mints M, Bertario L, Pineda M, Navarro M, Morak M, Renkonen-Sinisalo L, Valentin MD, Frayling IM, Plazzer J-P, Pylvanainen K, Genuardi M, Mecklin J-P, Moeslein G, Sampson JR, Capella G, Mallorca Group (2018) Cancer risk and survival in Path_MMR carriers by gene and gender up to 75 years of age: a report from the prospective Lynch syndrome database. Gut 67:1306–1316
Myrhøj T, Andersen M-B, Bernstein I (2008) Screening for urinary tract cancer with urine cytology in Lynch syndrome and Familial colorectal cancer. Fam Cancer 7:303–307
Burn J, Gerdes A-M, Macrae F, Mecklin J-P, Moeslein G, Olschwang S, Eccles D, Evans DG, Maher ER, Bertario L, Bisgaard M-L, Dunlop MG, Ho JWC, Hodgson SV, Lindblom A, Lubinski J, Morrison PJ, Murday V, Ramesar R, Side L, Scott RJ, Thomas HJW, Vasen HF, Barker G, Crawford G, Elliott F, Movahedi M, Pylvanainen K, Wijnen JT, Fodde R, Lynch HT, Mathers JC, Bishop DT, Investigators (2011) Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet 378, 2081–2087
Moreira L, Balaguer F, Lindor N, de la Chapelle A, Hampel H, Aaltonen LA, Hopper JL, Le Marchand L, Gallinger S, Newcomb PA, Haile R, Thibodeau SN, Gunawardena S, Jenkins MA, Buchanan DD, Potter JD, Baron JA, Ahnen DJ, Moreno V, Andreu M, de Leon P, Rustgi M, Castells AK (2012) EPICOLON consortium. Identification of Lynch syndrome among patients with colorectal cancer. JAMA 308:1555–1565
Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW (2015) & American College of Gastroenterology. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am. J. Gastroenterol. 110, 223–62; quiz 263
Lynch HT, de la Chapelle A (1999) Genetic susceptibility to non-polyposis colorectal cancer. J Med Genet 36:801–818
CAS PubMed PubMed Central Google Scholar
Plazzer JP, Sijmons RH, Woods MO, Peltomäki P, Thompson B, Dunnen D, J. T., Macrae F (2013) The insight database: utilizing 100 years of insights into Lynch syndrome. Fam Cancer 12:175–180
Thompson BA, Spurdle AB, Plazzer J-P, Greenblatt MS, Akagi K, Al-Mulla F, Bapat B, Bernstein I, Capellá G, den Dunnen JT, du Sart D, Fabre A, Farrell MP, Farrington SM, Frayling IM, Frebourg T, Goldgar DE, Heinen CD, Holinski-Feder E, Kohonen-Corish M, Robinson KL, Leung SY, Martins A, Moller P, Morak M, Nystrom M, Peltomaki P, Pineda M, Qi M, Ramesar R, Rasmussen LJ, Royer-Pokora B, Scott RJ, Sijmons R, Tavtigian SV, Tops CM, Weber T, Wijnen J, Woods MO, Macrae F, Genuardi M (2014) Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the insight locus-specific database. Nat Genet 46:107–115
Article CAS PubMed Google Scholar
Rehm HL, Berg JS, Brooks LD, Bustamante CD, Evans JP, Landrum MJ, Ledbetter DH, Maglott DR, Martin CL, Nussbaum RL, Plon SE, Ramos EM, Sherry ST, Watson MS (2015) ClinGen. ClinGen–the clinical genome resource. N Engl J Med 372:2235–2242
Article CAS PubMed PubMed Central Google Scholar
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, ACMG Laboratory Quality Assurance Committee (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet Med 17:405–424
Article PubMed PubMed Central Google Scholar
Rivera-Muñoz EA, Milko LV, Harrison SM, Azzariti DR, Kurtz CL, Lee K, Mester JL, Weaver MA, Currey E, Craigen W, Eng C, Funke B, Hegde M, Hershberger RE, Mao R, Steiner RD, Vincent LM, Martin CL, Plon SE, Ramos E, Rehm HL, Watson M, Berg JS (2018) ClinGen variant curation expert panel experiences and standardized processes for disease and gene-level specification of the ACMG/AMP guidelines for sequence variant interpretation. Hum Mutat 39:1614–1622
ClinVar ClinVar. at https://www.ncbi.nlm.nih.gov/clinvar/?term=VUS
Schmidt RJ (2020) Precision medicine in practice: molecular diagnosis enabling precision therapies, an issue of the clinics in laboratory medicine. Elsevier Health Sciences
Miosge LA, Field MA, Sontani Y, Cho V, Johnson S, Palkova A, Balakishnan B, Liang R, Zhang Y, Lyon S, Beutler B, Whittle B, Bertram EM, Enders A, Goodnow CC, Andrews TD (2015) Comparison of predicted and actual consequences of missense mutations. Proc Natl Acad Sci U S A 112:E5189–E5198
Article CAS PubMed PubMed Central Google Scholar
Rehm HL, Alaimo JT, Aradhya S, Bayrak-Toydemir P, Best H, Brandon R, Buchan JG, Chao EC, Chen E, Clifford J, Cohen ASA, Conlin LK, Das S, Davis KW, Del Gaudio D, Del Viso F, DiVincenzo C, Eisenberg M, Guidugli L, Hammer MB, Harrison SM, Hatchell KE, Dyer LH, Hoang LU, Holt JM, Jobanputra V, Karbassi ID, Kearney HM, Kelly MA, Kelly JM, Kluge ML, Komala T, Kruszka P, Lau L, Lebo MS, Marshall CR, McKnight D, McWalter K, Meng Y, Nagan N, Neckelmann CS, Neerman N, Niu Z, Paolillo VK, Paolucci SA, Perry D, Pesaran T, Radtke K, Rasmussen KJ, Retterer K, Saunders CJ, Spiteri E, Stanley C, Szuto A, Taft RJ, Thiffault I, Thomas BC, Thomas-Wilson A, Thorpe E, Tidwell TJ, Towne MC, Zouk H (2023) & Medical Genome Initiative Steering Committee. The landscape of reported VUS in multi-gene panel and genomic testing: Time for a change. Genet. Med. 25, 100947
Starita LM, Ahituv N, Dunham MJ, Kitzman JO, Roth FP, Seelig G, Shendure J, Fowler DM (2017) Variant interpretation: functional assays to the rescue. Am J Hum Genet 101:315–325
Article CAS PubMed PubMed Central Google Scholar
Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, Maglott DR (2014) ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res 42:D980–D985
Article CAS PubMed Google Scholar
Landrum MJ, Lee JM, Benson M, Brown G, Chao C, Chitipiralla S, Gu B, Hart J, Hoffman D, Hoover J, Jang W, Katz K, Ovetsky M, Riley G, Sethi A, Tully R, Villamarin-Salomon R, Rubinstein W, Maglott DR (2016) ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res 44:D862–D868
Article CAS PubMed Google Scholar
Deans ZC, Ahn JW, Carreira IM, Dequeker E, Henderson M, Lovrecic L, Õunap K, Tabiner M, Treacy R, van Asperen (2022) C. J. Recommendations for reporting results of diagnostic genomic testing. Eur J Hum Genet 30, 1011–1016
Idos G, Valle L (2021) GeneReviews® [Internet]. University of Washington, Seattle
Plazzer JP, Macrae F, Yin X, Thompson BA, Farrington SM, Currie L, Lagerstedt-Robinson K, Frederiksen JH, van Overeem Hansen T, Graversen L, Frayling IM, Akagi K, Yamamoto G, Al-Mulla F, Ferber MJ, Martins A, Genuardi M, Kohonen-Corish M, Baert-Desurmont S, Spurdle AB, Capellá G, Pineda M, Woods MO, Rasmussen LJ, Heinen CD, Scott RJ, Tops CM, Greenblatt MS, Dominguez-Valentin M, Ognedal E, Borras E, Leung SY, Mahmood K, Holinski-Feder E, Laner A (2024) Mismatch repair gene specifications to the ACMG/AMP classification criteria: Consensus recommendations from the InSiGHT ClinGen Hereditary Colorectal Cancer / Polyposis Variant Curation Expert Panel. bioRxivhttps://doi.org/10.1101/2024.05.13.24307108
Thompson BA, Goldgar DE, Paterson C, Clendenning M, Walters R, Arnold S, Parsons MT, Michael D, Gallinger W, Haile S, Hopper RW, Jenkins JL, Lemarchand MA, Lindor L, Newcomb NM, Thibodeau PA, Registry SNCCF, Young JP, Buchanan DD, Tavtigian SV, Spurdle (2013) A. B. 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 34:200–209
Tavtigian SV, Greenblatt MS, Harrison SM, Nussbaum RL, Prabhu SA, Boucher KM, Biesecker LG (2018) ClinGen sequence variant interpretation working group (ClinGen SVI). Modeling the ACMG/AMP variant classification guidelines as a bayesian classification framework. Genet Med 20:1054–1060
Article PubMed PubMed Central Google Scholar
Parsons MT, de la Hoya M, Richardson ME, Tudini E, Anderson M, Berkofsky-Fessler W, Caputo SM, Chan RC, Cline MS, Feng B-J, Fortuno C, Gomez-Garcia E, Hadler J, Hiraki S, Holdren M, Houdayer C, Hruska K, James P, Karam R, Leong HS, Martins A, Mensenkamp AR, Monteiro AN, Nathan V, O’Connor R, Pedersen IS, Pesaran T, Radice P, Schmidt G, Southey M, Tavtigian S, Thompson BA, Toland AE, Turnbull C, Vogel MJ, Weyandt J, Wiggins GAR, Zec L, Couch FJ, Walker LC, Vreeswijk MPG, Goldgar DE (2024) Spurdle, A. B. Evidence-based recommendations for gene-specific ACMG/AMP variant classification from the ClinGen ENIGMA BRCA1 and BRCA2 variant curation expert panel. Am J Hum Genet 111:2044–2058
Houlleberghs H, Dekker M, Lantermans H, Kleinendorst R, Dubbink HJ, Hofstra RMW, Verhoef S, Te Riele H (2016) Oligonucleotide-directed mutagenesis screen to identify pathogenic Lynch syndrome-associated MSH2 DNA mismatch repair gene variants. Proc. Natl. Acad. Sci. U. S. A. 113, 4128–4133
Tricarico R, Kasela M, Mareni C, Thompson BA, Drouet A, Staderini L, Gorelli G, Crucianelli F, Ingrosso V, Kantelinen J, Papi L, De Angioletti M, Berardi M, Gaildrat P, Soukarieh O, Turchetti D, Martins A, Spurdle AB, Nyström M, Genuardi M (2017) Assessment of the insight interpretation criteria for the clinical classification of 24 MLH1 and MSH2 gene variants. Hum Mutat 38:64–77& InSiGHT Variant Interpretation Committee
Rasmussen LJ, Heinen CD, Royer-Pokora B, Drost M, Tavtigian S, Hofstra RMW, de Wind N (2012) Pathological assessment of mismatch repair gene variants in Lynch syndrome: past, present, and future. Hum Mutat 33:1617–1625
Article CAS PubMed Google Scholar
Peña-Diaz J, Rasmussen LJ (2016) Approaches to diagnose DNA mismatch repair gene defects in cancer. DNA Repair 38:147–154
Drost M, Tiersma Y, Thompson BA, Frederiksen JH, Keijzers G, Glubb D, Kathe S, Osinga J, Westers H, Pappas L, Boucher KM, Molenkamp S, Zonneveld JB, van Asperen CJ, Goldgar DE, Wallace SS, Sijmons RH, Spurdle AB, Rasmussen LJ, Greenblatt MS, de Wind N, Tavtigian SV (2019). A functional assay-based procedure to classify mismatch repair gene variants in Lynch syndrome. Genet Med 21:1486–1496
Article CAS PubMed Google Scholar
Drost M, Tiersma Y, Glubb D, Kathe S, van Hees S, Calléja F, Zonneveld JBM, Boucher KM, Ramlal RPE, Thompson BA, Rasmussen LJ, Greenblatt MS, Lee A, Spurdle AB, Tavtigian SV (2020) & de wind, N. Two integrated and highly predictive functional analysis-based procedures for the classification of MSH6 variants in Lynch syndrome. Genet Med 22:847–856
Article CAS PubMed PubMed Central Google Scholar
Rayner E, Tiersma Y, Fortuno C, van Hees-Stuivenberg S, Drost M, Thompson B, Spurdle AB (2022) Wind, N. Predictive functional assay-based classification of PMS2 variants in Lynch syndrome. Hum Mutat 43:1249–1258de
Article CAS PubMed Google Scholar
Bouras A, Lefol C, Ruano E, Grand-Masson C, Auclair-Perrossier J, Wang Q (2024) Splicing analysis of 24 potential spliceogenic variants in MMR genes and clinical interpretation based on refined ACMG/AMP criteria. Hum Mol Genet 33:850–859
Fowler DM, Fields S (2014) Deep mutational scanning: a new style of protein science. Nat Methods 11:801–807
Jia X, Burugula BB, Chen V, Lemons RM, Jayakody S, Maksutova M, Kitzman JO (2021) Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk. Am J Hum Genet 108:163–175
Ollodart AR, Yeh C-LC, Miller AW, Shirts BH, Gordon AS, Dunham MJ (2021) Multiplexing mutation rate assessment: determining pathogenicity of Msh2 variants in Saccharomyces cerevisiae. Genetics 218
Gammie AE, Erdeniz N, Beaver J, Devlin B, Nanji A, Rose MD (2007) Functional characterization of pathogenic human MSH2 missense mutations in Saccharomyces cerevisiae. Genetics 177:707–721
Scott A, Hernandez F, Chamberlin A, Smith C, Karam R, Kitzman JO (2022) Saturation-scale functional evidence supports clinical variant interpretation in Lynch syndrome. Genome Biol 23:266
Hopf TA, Ingraham JB, Poelwijk FJ, Schärfe CPI, Springer M, Sander C, Marks DS (2017) Mutation effects predicted from sequence co-variation. Nat Biotechnol 35:128–135
Cagiada M, Johansson KE, Valanciute A, Nielsen SV, Hartmann-Petersen R, Yang JJ, Fowler DM, Stein A, Lindorff-Larsen K (2021) Understanding the origins of loss of protein function by analyzing the effects of thousands of variants on activity and abundance. Mol Biol Evol 38:3235–3246
Chiasson MA, Rollins NJ, Stephany JJ, Sitko KA, Matreyek KA, Verby M, Sun S, Roth FP, DeSloover D, Marks DS, Rettie AE, Fowler DM (2020) Multiplexed measurement of variant abundance and activity reveals VKOR topology, active site and human variant impact. Elife 9
Livesey BJ, Marsh JA (2020) Using deep mutational scanning to benchmark variant effect predictors and identify disease mutations. Mol Syst Biol 16:e9380
Frazer J, Notin P, Dias M, Gomez A, Min JK, Brock K, Gal Y, Marks DS (2021) Disease variant prediction with deep generative models of evolutionary data. Nature 599:91–95
Rath A, Radecki AA, Rahman K, Gilmore RB, Hudson JR, Cenci M, Tavtigian SV, Grady JP, Heinen C (2022) D. A calibrated cell-based functional assay to aid classification of MLH1 DNA mismatch repair gene variants. Hum Mutat 43:2295–2307
Bouvet D, Bodo S, Munier A, Guillerm E, Bertrand R, Colas C, Duval A, Coulet F, Muleris M (2019) Methylation Tolerance-Based functional assay to assess variants of unknown significance in the MLH1 and MSH2 genes and identify patients with Lynch syndrome. Gastroenterology 157:421–431
Article CAS PubMed Google Scholar
Dunham WH, Mullin M, Gingras A-C (2012) Affinity-purification coupled to mass spectrometry: basic principles and strategies. Proteomics 12:1576–1590
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