Epigenetic mechanisms in the pathogenesis of Lynch syndrome

Clinical Genetics

Volumn 85, Issue 5, 2014, Pages 403-412

  Peltomaki P ^a  

^a UNIVERSITY OF HELSINKI   (Finland)

Author keywords

DNA mismatch repair genes; EPCAM; Epimutation; Lynch syndrome; Methylation; Microsatellite instability; MLH1; MSH2; Mutation

Indexed keywords

MISMATCH REPAIR PROTEIN PMS2; PROTEIN MLH1; PROTEIN MSH2; PROTEIN MSH6; ADENOSINE TRIPHOSPHATASE; DNA BINDING PROTEIN; G-T MISMATCH-BINDING PROTEIN; MLH1 PROTEIN, HUMAN; MSH2 PROTEIN, HUMAN; NUCLEAR PROTEIN; PMS2 PROTEIN, HUMAN; POLYDEOXYRIBONUCLEOTIDE SYNTHASE; SIGNAL TRANSDUCING ADAPTOR PROTEIN;

ARTICLE; DISEASE PREDISPOSITION; EPIGENETICS; GENE MUTATION; GENETIC ASSOCIATION; HEREDITARY NONPOLYPOSIS COLORECTAL CANCER; HUMAN; MISMATCH REPAIR; PATHOGENESIS; PRIORITY JOURNAL; TUMOR SUPPRESSOR GENE; DNA METHYLATION; GENETIC EPIGENESIS; GENETIC PREDISPOSITION; GENETICS; GERMLINE MUTATION; METABOLISM; PATHOLOGY;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ADENOSINE TRIPHOSPHATASES; COLORECTAL NEOPLASMS, HEREDITARY NONPOLYPOSIS; DNA METHYLATION; DNA MISMATCH REPAIR; DNA REPAIR ENZYMES; DNA-BINDING PROTEINS; EPIGENESIS, GENETIC; GENETIC PREDISPOSITION TO DISEASE; GERM-LINE MUTATION; HUMANS; MUTS HOMOLOG 2 PROTEIN; NUCLEAR PROTEINS;

EID: 84897400369     PISSN: 00099163     EISSN: 13990004     Source Type: Journal    
DOI: 10.1111/cge.12349     Document Type: Article

References (96)

1. Vasen HF, Mecklin JP, Khan PM, Lynch HT. The international collaborative group on hereditary non-polyposis colorectal cancer (ICG-HNPCC). Dis Colon Rectum 1991: 34: 424-425.
2. 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.
3. Umar A, Boland CR, Terdiman JP et al. Revised Bethesda guidelines for hereditary non-polyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 2004: 96: 261-268.
4. Cohen PR, Kohn SR, Kurzrock R. Association of sebaceous gland tumors and internal malignancy: the Muir-Torre syndrome. Am J Med 1991: 90: 606-613.
5. Wimmer K, Etzler J. Constitutional mismatch repair-deficiency syndrome: have we so far seen only the tip of an iceberg? Hum Genet 2008: 124: 105-122.
6. Turcot J, Despres JP, St PF. Malignant tumors of the central nervous system associated with familial polyposis of the colon: report of two cases. Dis Colon Rectum 1959: 2: 465-468.
7. Aaltonen LA, Salovaara R, Kristo P et al. Incidence of hereditary nonpolyposis colorectal cancer and molecular screening for the disease. N Engl J Med 1998: 338: 1481-1487.
8. Samowitz WS, Curtin K, Lin HH et al. The colon cancer burden of genetically defined hereditary nonpolyposis colon cancer. Gastroenterology 2001: 121: 830-838.
9. Ollikainen M, Abdel-Rahman WM, Moisio A-L et al. Molecular analysis of familial endometrial carcinoma: a manifestation of hereditary nonpolyposis colorectal cancer or a separate syndrome? J Clin Oncol 2005: 23: 4609-4616.
10. Hampel H, de la Chapelle A. How do we approach the goal of identifying everybody with Lynch syndrome? Fam Cancer 2013: 12: 313-317.
11. Warthin AS. Heredity with reference to carcinoma. Arch Intern Med 1913: 12: 546-555.
12. Peltomäki P, Aaltonen LA, Sistonen P et al. Genetic mapping of a locus predisposing to human colorectal cancer. Science 1993: 260: 810-812.
13. Thompson BA, Spurdle AB, Plazzer J-P et al. Application of a five-tiered scheme for standardized classification of 2, 360 unique mismatch repair gene variants lodged on the InSiGHT locus-specific database. Nat Genet 2014: 46: 107-115.
14. Gazzoli I, Loda M, Garber J, Syngal S, Kolodner RD. A hereditary nonpolyposis colorectal carcinoma case associated with hypermethylation of the MLH1 gene in normal tissue and loss of heterozygosity of the unmethylated allele in the resulting microsatellite instability-high tumor. Cancer Res 2002: 62: 3925-3928.
15. Wong JJ, Hawkins NJ, Ward RL. Colorectal cancer: a model for epigenetic tumorigenesis. Gut 2007: 56: 140-148.
16. Wilson BG, Roberts CW. SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer 2011: 11: 481-492.
17. 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.
18. Li GM. Mechanisms and functions of DNA mismatch repair. Cell Res 2008: 18: 85-98.
19. Kansikas M, Kariola R, Nyström M. Verification of the three step model in assessing the pathogenicity of mismatch repair gene variants. Hum Mutat 2011: 32: 107-115.
20. Fishel R. The selection for mismatch repair defects in hereditary nonpolyposis colorectal cancer: revising the mutator hypothesis. Cancer Res 2001: 61: 7369-7374.
21. Knudson AG Jr. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A 1971: 68: 820-823.
22. Ollikainen M, Hannelius U, Lindgren CM, Abdel-Rahman WM, Kere J, Peltomäki P. Mechanisms of inactivation of MLH1 in hereditary nonpolyposis colorectal carcinoma: a novel approach. Oncogene 2007: 26: 4541-4549.
23. Zhang J, Lindroos A, Ollila S et al. Gene conversion is a frequent mechanism of inactivation of the wild-type allele in cancers from MLH1/MSH2 deletion carriers. Cancer Res 2006: 66: 659-664.
24. Nagasaka T, Rhees J, Kloor M et al. Somatic hypermethylation of MSH2 is a frequent event in Lynch Syndrome colorectal cancers. Cancer Res 2010: 70: 3098-3108.
25. Beggs AD, Jones A, El-Bahwary M, Abulafi M, Hodgson SV, Tomlinson IP. Whole-genome methylation analysis of benign and malignant colorectal tumours. J Pathol 2013: 229: 697-704.
26. The Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012: 487: 330-337.
27. Berger AH, Pandolfi PP. Haploinsufficiency: a driving force in cancer. J Pathol 2011: 223: 137-146.
28. Cejka P, Stojic L, Mojas N et al. Methylation-induced G(2)/M arrest requires a full complement of the mismatch repair protein hMLH1. EMBO J 2003: 22: 2245-2254.
29. Vasen HFA, Stormorken A, Menko FH et al. MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families. J Clin Oncol 2001: 19: 4074-4080.
30. Baglietto L, Lindor NM, Dowty JG et al. Risks of Lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst 2010: 102: 193-201.
31. Senter L, Clendenning M, Sotamaa K et al. The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology 2008: 135: 419-428.
32. Engel C, Loeffler M, Steinke V et al. Risks of less common cancers in proven mutation carriers with Lynch syndrome. J Clin Oncol 2012: 30: 4409-4415.
33. Peltomäki P, Gao X, Mecklin J-P. Genotype and phenotype in hereditary nonpolyposis colon cancer: a study of families with different vs. shared predisposing mutations. Fam Cancer 2001: 1: 9-15.
34. Pande M, Chen J, Amos CI, Lynch PM, Broaddus R, Frazier ML. Influence of methylenetetrahydrofolate reductase gene polymorphisms C677T and A1298C on age-associated risk for colorectal cancer in a Caucasian Lynch syndrome population. Cancer Epidemiol Biomarkers Prev 2007: 16: 1753-1759.
35. Park J-G, Park YJ, Wijnen JT, Vasen HFA. Gene-environment interaction in hereditary non-polyposis colorectal cancer with implications for diagnosis and genetic testing. Int J Cancer 1999: 82: 516-519.
36. van Duijnhoven FJB, Botma A, Winkels R, Nagengast FM, Vasen HFA, Kampman E. Do lifestyle factors influence colorectal cancer risk in Lynch syndrome? Fam Cancer 2013: 12: 285-293.
37. Tammen SA, Frisco S, Choi S-W. Epigenetics: the link between nature and nurture. Mol Aspects Med 2013: 34: 753-764.
38. Pritchard CC, Smith C, Salipante SJ et al. ColoSeq provides comprehensive Lynch and polyposis syndrome mutational analysis using massively parallel sequencing. J Mol Diagn 2012: 14: 357-366.
39. Lagerstedt Robinson K, Liu T et al. Lynch syndrome (Hereditary nonpolyposis colorectal cancer) diagnostics in 2006. J Natl Cancer Inst 2007: 99: 291-299.
40. Nyström-Lahti M, Wu Y, Moisio A-L et al. DNA mismatch repair gene mutations in 55 verified or putative kindreds with hereditary non-polyposis colorectal cancer. Hum Mol Genet 1996: 5: 763-769.
41. Wijnen J, Khan PM, Vasen H et al. Hereditary nonpolyposis colorectal cancer families not complying with the Amsterdam criteria show extremely low frequency of mismatch repair gene mutations. Am J Hum Genet 1997: 61: 329-335.
42. Pineda M, Mur P, Iniesta MD et al. MLH1 methylation screening is effective in identifying epimutation carriers. Eur J Hum Genet 2012: 20: 1256-1264.
43. Kwok CT, Ward RL, Hawkins NJ, Hitchins MP. Detection of allelic imbalance in MLH1 expression by pyrosequencing serves as a tool for the identification of germline defects in Lynch syndrome. Fam Cancer 2010: 9: 345-356.
44. Whitelaw NC, Whitelaw E. Transgenerational epigenetic inheritance in health and disease. Curr Opin Genet Dev 2008: 18: 273-279.
45. Suter CM, Martin DI, Ward RL. Germline epimutation of MLH1 in individuals with multiple cancers. Nat Genet 2004: 36: 497-501.
46. Gylling A, Ridanpää M, Vierimaa O et al. Large genomic rearrangements and germline epimutations in Lynch syndrome. Int J Cancer 2009: 124: 2333-2340.
47. Hitchins MP, Rapkins RW, Kwok CT et al. Dominantly inherited constitutional epigenetic silencing of MLH1 in a cancer-affected family is linked to a single nucleotide variant within the 5'UTR. Cancer Cell 2011: 20: 200-213.
48. Morak M, Koehler U, Schackert HK et al. Biallelic MLH1 SNP cDNA expression or constitutional promoter methylation can hide genomic rearrangements causing Lynch syndrome. J Med Genet 2011: 48: 513-519.
49. Hitchins MP. The role of epigenetics in Lynch syndrome. Fam Cancer 2013: 12: 189-205.
50. Hitchins M, Williams R, Cheong K et al. MLH1 germline epimutations as a factor in hereditary nonpolyposis colorectal cancer. Gastroenterology 2005: 129: 1392-1399.
51. Morak M, Schackert HK, Rahner N et al. Further evidence for heritability of an epimutation in one of 12 cases with MLH1 promoter methylation in blood cells displaying HNPCC. Eur J Hum Genet 2008: 16: 804-811.
52. Chan TL, Yuen ST, Kong CK et al. Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer. Nat Genet 2006: 38: 1178-1183.
53. Ligtenberg MJ, Kuiper RP, Chan TL et al. Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1. Nat Genet 2009: 41: 112-117.
54. Tutlewska K, Lubinski J, Kurzawski G. Germline deletions in the EPCAM gene as a cause of Lynch syndrome - literature review. Hered Cancer Clin Pract 2013: 11: 9.
55. Ligtenberg MJL, Kuiper RP, van Kessel AG, Hoogerbrugge N. EPCAM deletion carriers constitute a unique subgroup of Lynch syndrome patients. Fam Cancer 2013: 12: 169-174.
56. Huth C, Kloor M, Voigt AY et al. The molecular basis of EPCAM expression loss in Lynch syndrome-associated tumors. Mod Pathol 2012: 25: 911-916.
57. Hitchins MP, Wong JJ, Suthers G et al. Inheritance of a cancer-associated MLH1 germ-line epimutation. N Engl J Med 2007: 356: 697-705.
58. Kwok CT, Vogelaar IP, van Zelst-Stams WA et al. The MLH1 c.-27C>A and c.85G>T variants are linked to dominantly inherited MLH1 epimutation and are borne on a European ancestral haplotype. Eur J Hum Genet 2013 doi: 10.1038/ejhg.2013.200 [Epub ahead of print].
59. Kempers MJE, Kuiper R, Ockeloen CW et al. Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study. Lancet Oncol 2011: 12: 49-55.
60. Ward RL, Dobbins T, Lindor NM, Rapkins RW, Hitchins MP. Identification of constitutional MLH1 epimutations and promoter variants in colorectal cancer patients from the Colon Cancer Family Registry. Genet Med 2013: 15: 25-35.
61. Niessen RC, Hofstra RMW, Westers H et al. Germline hypermethylation of MLH1 and EPCAM deletions are a frequent cause of Lynch syndrome. Genes Chromosomes Cancer 2009: 48: 737-744.
62. Lynch HT, Krush AJ. Cancer family "G" revisited: 1895-1970. Cancer 1971: 27: 1505-1511.
63. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 2006: 24: 2137-2150.
64. da Silva FC, de Oliveira LP, Santos EM et al. Frequency of extracolonic tumors in Brazilian families with Lynch syndrome: analysis of a hereditary colorectal cancer institutional registry. Fam Cancer 2010: 9: 563-570.
65. Chao E, Lipkin SM. Molecular models for the tissue specificity of DNA mismatch repair-deficient carcinogenesis. Nucleic Acids Res 2006: 34: 840-852.
66. Lotsari JE, Gylling A, Abdel-Rahman WM et al. Breast carcinoma and Lynch syndrome - Molecular analysis of tumors arising in mutation carriers, non-carriers, and sporadic cases. Breast Cancer Res 2012: 14: R90.
67. Niskakoski A, Kaur S, Renkonen-Sinisalo L et al. Distinct molecular profiles in Lynch syndrome-associated and sporadic ovarian carcinomas. Int J Cancer 2013: 133: 2596-2608.
68. Giuffre G, Müller A, Brodegger T et al. Microsatellite analysis of hereditary nonpolyposis colorectal cancer-associated colorectal adenomas by laser-assisted microdissection: correlation with mismatch repair protein expression provides new insights in early steps of tumorigenesis. J Mol Diagn 2005: 7: 160-170.
69. Watson P, Riley B. The tumor spectrum in the Lynch syndrome. Fam Cancer 2005: 4: 245-248.
70. Aarnio M, Sankila R, Pukkala E et al. Cancer risk in mutation carriers of DNA mismatch repair genes. Int J Cancer 1999: 81: 214-218.
71. Win AK, Young JP, Lindor NM et al. Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: a prospective cohort study. J Clin Oncol 2012: 30: 958-964.
72. Weisenberger DJ, Siegmund KD, Campan M et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet 2006: 38: 787-793.
73. Domingo E, Laiho P, Ollikainen M et al. BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing. J Med Genet 2004: 41: 664-668.
74. Balaguer F, Moreira L, Lozano JJ et al. Colorectal cancers with microsatellite instability display unique miRNA profiles. Clin Cancer Res 2011: 17: 6239-6249.
75. Joensuu EI, Abdel-Rahman WM, Ollikainen M, Ruosaari S, Knuutila S, Peltomäki P. Epigenetic signatures of familial cancer are characteristic of tumor type and family category. Cancer Res 2008: 68: 4597-4605.
76. Gylling A, Abdel-Rahman WM, Juhola M et al. Is gastric cancer part of the tumor spectrum of hereditary nonpolyposis colorectal cancer? - A molecular genetic study. Gut 2007: 56: 926-933.
77. Esteller M, Fraga MF, Guo M et al. DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis. Hum Mol Genet 2001: 10: 3001-3007.
78. Pavicic W, Perkiö E, Kaur S, Peltomäki P. Altered methylation at microRNA-associated CpG islands in hereditary and sporadic carcinomas: MS-MLPA-based approach. Mol Med 2011: 17: 726-735.
79. Gylling A, Nieminen TT, Abdel-Rahman WM et al. Differential cancer predisposition in Lynch syndrome: insights from molecular analysis of brain and urinary tract tumors. Carcinogenesis 2008: 29: 1351-1359.
80. Woerner SM, Benner A, Sutter C et al. Pathogenesis of DNA repair-deficient cancers: a statistical meta-analysis of putative real common target genes. Oncogene 2003: 22: 2226-2235.
81. Kuismanen SA, Moisio A-L, Schweizer P et al. Endometrial and colorectal tumors from patients with hereditary nonpolyposis colon cancer display different patterns of microsatellite instability. Am J Pathol 2002: 160: 1953-1958.
82. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW. Cancer genome landscapes. Science 2013: 339: 1546-1558.
83. Legolvan MP, Taliano RJ, Resnick MB. Application of molecular techniques in the diagnosis, prognosis and management of patients with colorectal cancer: a practical approach. Hum Pathol 2012: 43: 1157-1168.
84. Ward RL, Hicks S, Hawkins NJ. Population-based molecular screening for Lynch syndrome: implications for personalized medicine. J Clin Oncol 2013: 31: 2554-2562.
85. Deng G, Chen A, Hong J, Chae HS, Kim YS. Methylation of CpG in a small region of the hMLH1 promoter invariably correlates with the absence of gene expression. Cancer Res 1999: 59: 2029-2033.
86. 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.
87. Gausachs M, Mur P, Corral J et al. MLH1 promoter hypermethylation in the analytical algorithm of Lynch syndrome: a cost-effectiveness study. Eur J Hum Genet 2012: 20: 762-768.
88. Rahner N, Friedrichs N, Steinke V et al. Coexisting somatic promoter hypermethylation and pathogenic MLH1 germline mutation in Lynch syndrome. J Pathol 2008: 214: 10-16.
89. Bettstetter M, Dechant S, Ruemmele P et al. Distinction of hereditary nonpolyposis colorectal cancer and sporadic microsatellite-unstable colorectal cancer through quantification of MLH1 methylation by real-time PCR. Clin Cancer Res 2007: 13: 3221-3228.
90. Vasen HF, Blanco I, Aktan-Collan K et al. Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts. Gut 2013: 62: 812-823.
91. Heyn H, Esteller M. DNA methylation profiling in the clinic: applications and challenges. Nat Rev Genet 2012: 13: 679-692.
92. Nieminen TT, Gylling A, Abdel-Rahman WM et al. Molecular analysis of endometrial tumorigenesis: importance of complex hyperplasia regardless of atypia. Clin Cancer Res 2009: 15: 5772-5783.
93. Hewish M, Lord CJ, Martin SA, Cunningham D, Ashworth A. Mismatch repair deficient colorectal cancer in the era of personalized treatment. Nat Rev Clin Oncol 2010: 7: 197-208.
94. Jover R, Nguyen T-P, Perez-Carbonell L et al. 5-fluorouracil adjuvant chemotherapy does not increase survival in patients with CpG island methylator phenotype colorectal cancer. Gastroenterology 2011: 140: 1174-1181.
95. Donada M, Bonin S, Pettirosso D, Stanta G. Management of stage II colon cancer - the use of molecular biomarkers for adjuvant therapy decision. BMC Gastroenterol 2013: 13: 36.
96. Heijink DM, de Vries EGE, Koornstra JJ et al. Perspectives for tailored chemoprevention and treatment of colorectal cancer in Lynch syndrome. Crit Rev Oncol Hematol 2011: 80: 264-277.