Low-level APC mutational mosaicism is the underlying cause in a substantial fraction of unexplained colorectal adenomatous polyposis cases

Journal of Medical Genetics

Volumn 53, Issue 3, 2016, Pages 172-179

  Spier, Isabel ^a   Drichel, Dmitriy ^b   Kerick, Martin ^c,d   Kirfel, Jutta ^a   Horpaopan, Sukanya ^a,e   Laner, Andreas ^f,g   Holzapfel, Stefanie ^a   Peters, Sophia ^a   Adam, Ronja ^a   Zhao, Bixiao ^h   Becker, Tim ^a,b   Lifton, Richard P ^h   Perner, Sven ⁱ   Hoffmann, Per ^a,j   Kristiansen, Glen ^a   Timmermann, Bernd ^c   Nöthen, Markus M ^a   Holinski Feder, Elke ^f,g   Schweiger, Michal R ^c,d   Aretz, Stefan ^a  

^a UNIVERSITY OF BONN   (Germany)

^b GERMAN CENTER FOR NEURODEGENERATIVE DISEASES DZNE   (Germany)

^c MAX PLANCK INSTITUTE FOR MOLECULAR GENETICS   (Germany)

^d UNIVERSITY OF COLOGNE   (Germany)

^e NARESUAN UNIVERSITY   (Thailand)

^f LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^g MGZ Center of Medical Genetics   (Germany)

^h YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

ⁱ UNIVERSITY HOSPITAL BONN   (Germany)

^j UNIVERSITY HOSPITAL BASEL   (Switzerland)

more..

Author keywords

[No Author keywords available]

Indexed keywords

APC PROTEIN;

ADENOMATOUS POLYP; ARTICLE; COLORECTAL ADENOMA; COLORECTAL ADENOMATOUS POLYPOSIS; COLORECTAL CARCINOMA; COLORECTAL POLYP; GENE FREQUENCY; GENE MUTATION; HIGH THROUGHPUT SEQUENCING; INDEL MUTATION; LOSS OF FUNCTION MUTATION; MOSAICISM; PRIORITY JOURNAL; SOMATIC MUTATION; ADOLESCENT; ADULT; COLON POLYPOSIS; COLORECTAL TUMOR; GENETICS; HUMAN; MIDDLE AGED; MUTATION; MUTATION RATE; TUMOR SUPPRESSOR GENE;

ADENOMATOUS POLYPOSIS COLI; ADOLESCENT; ADULT; COLORECTAL NEOPLASMS; GENES, APC; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; MIDDLE AGED; MUTATION; MUTATION RATE;

EID: 84960092546     PISSN: 00222593     EISSN: 14686244     Source Type: Journal    
DOI: 10.1136/jmedgenet-2015-103468     Document Type: Article

References (40)

1. Galiatsatos P, Foulkes WD. Familial adenomatous polyposis. Am J Gastroenterol 2006;101:385-98.
2. Mazzei F, Viel A, Bignami M. Role of MUTYH in human cancer. Mutat Res 2013;743-744:33-43.
3. Palles C, Cazier J-B, Howarth KM, Domingo E, Jones AM, Broderick P, Kemp Z, Spain SL, Almeida EG, Salguero I, Sherborne A, Chubb D, Carvajal-Carmona LG, Ma Y, Kaur K, Dobbins S, Barclay E, Gorman M, Martin L, Kovac MB, Humphray S, Thomas HJW, Maher E, Evans G, Lucassen A, Cummings C, Stevens M, Walker L, Halliday D, Armstrong R, Paterson J, Hodgson S, Homfray T, Side L, Izatt L, Donaldson A, Tomkins S, Morrison P, Goodman S, Brewer C, Henderson A, Davidson R, Murday V, Cook J, Haites N, Bishop T, Sheridan E, Green A, Marks C, Carpenter S, Broughton M, Greenhalge L, Suri M, Donnelly P, Bell J, Bentley D, Mcvean G, Ratcliffe P, Taylor J, Wilkie A, Donnelly P, Broxholme J, Buck D, Cazier J-B, Cornall R, Gregory L, Knight J, Lunter G, Mcvean G, Taylor J, Tomlinson I, Wilkie A, Buck D, Gregory L, Humphray S, Kingsbury Z, Mcvean G, Donnelly P, Cazier J-B, Broxholme J, Grocock R, Hatton E, Holmes CC, Hughes L, Humburg P, Kanapin A, Lunter G, Murray L, Rimmer A, Lucassen A, Holmes CC, Bentley D, Donnelly P, Taylor J, Petridis C, Roylance R, Sawyer EJ, Kerr DJ, Clark S, Grimes J, Kearsey SE, Thomas HJW, Mcvean G. Houlston RS, Tomlinson I, Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet 2013;45:136-44.
4. Friedl W, Aretz S. Familial adenomatous polyposis: experience from a study of 1164 unrelated german polyposis patients. Hered Cancer Clin Pract 2005;3:95-114.
5. Lagarde A, Rouleau E, Ferrari A, Noguchi T, Qiu J, Briaux A, Bourdon V, Remy V, Gaildrat P, Adelaide J, Birnbaum D, Lidereau R, Sobol H, Olschwang S. Germline APC mutation spectrum derived from 863 genomic variations identified through a 15-year medical genetics service to French patients with FAP. J Med Genet 2010;47:721-2.
6. Aretz S, Uhlhaas S, Goergens H, Siberg K, Vogel M, Pagenstecher C, Mangold E, Caspari R, Propping P, Friedl W. MUTYH-associated polyposis: 70 of 71 patients with biallelic mutations present with an attenuated or atypical phenotype. Int J Cancer 2006;119:807-14.
7. Grover S, Kastrinos F, Steyerberg EW, Cook EF, Dewanwala A, Burbidge LA, Wenstrup RJ, Syngal S. Prevalence and phenotypes of APC and MUTYH mutations in patients with multiple colorectal adenomas. JAMA 2012;308:485-92.
8. Nielsen M, Hes FJ, Nagengast FM, Weiss MM, Mathus-Vliegen EM, Morreau H, Breuning MH, Wijnen JT, Tops CMJ, Vasen HFA. Germline mutations in APC and MUTYH are responsible for the majority of families with attenuated familial adenomatous polyposis. Clin Genet 2007;71:427-33.
9. Spier I, Holzapfel S, Altmüller J, Zhao B, Horpaopan S, Vogt S, Chen S, Morak M, Raeder S, Kayser K, Stienen D, Adam R, Nürnberg P, Plotz G, Holinski-Feder E, Lifton RP, Thiele H, Hoffmann P, Steinke V, Aretz S. Frequency and phenotypic spectrum of germline mutations in POLE and seven other polymerase genes in 266 patients with colorectal adenomas and carcinomas. Int J Cancer 2015;137:320-31.
10. Spier I, Horpaopan S, Vogt S, Uhlhaas S, Morak M, Stienen D, Draaken M, Ludwig M, Holinski-Feder E, Nöthen MM, Hoffmann P, Aretz S. Deep intronic APC mutations explain a substantial proportion of patients with familial or early-onset adenomatous polyposis. Hum Mutat 2012;33:1045-50.
11. Azzopardi D, Dallosso AR, Eliason K, Hendrickson BC, Jones N, Rawstorne E, Colley J, Moskvina V, Frye C, Sampson JR, Wenstrup R, Scholl T, Cheadle JP. Multiple rare nonsynonymous variants in the adenomatous polyposis coli gene predispose to colorectal adenomas. Cancer Res 2008;68:358-63.
12. Lefevre JH, Bonilla C, Colas C, Winney B, Johnstone E, Tonks S, Day T, Hutnik K, Boumertit A, Soubrier F, Midgley R, Kerr D, Parc Y, Bodmer WF. Role of rare variants in undetermined multiple adenomatous polyposis and early-onset colorectal cancer. J Hum Genet 2012;57:709-16.
13. Will O, Carvajal-Carmona LG, Gorman P, Howarth KM, Jones AM, Polanco-Echeverry GM, Chinaleong J-A, Günther T, Silver A, Clark SK, Tomlinson I. Homozygous PMS2 deletion causes a severe colorectal cancer and multiple adenoma phenotype without extraintestinal cancer. Gastroenterology 2007;132:527-30.
14. Rio Frio T, Lavoie J, Hamel N, Geyer FC, Kushner YB, Novak DJ, Wark L, Capelli C, Reis-Filho JS, Mai S, Pastinen T, Tischkowitz MD, Marcus VA, Foulkes WD. Homozygous BUB1B mutation and susceptibility to gastrointestinal neoplasia. N Engl J Med 2010;363:2628-37.
15. de Voer RM, Geurts van Kessel A, Weren RDA, Ligtenberg MJL, Smeets D, Fu L, Vreede L, Kamping EJ, Verwiel ET, Hahn MM, Ariaans M, Spruijt L, Van Essen T, Houge G, Schackert HK, Sheng JQ, Venselaar H, van Ravenswaaij-Arts CM, Van Krieken JH, Hoogerbrugge N, Kuiper RP. Germline mutations in the spindle assembly checkpoint genes BUB1 and BUB3 are risk factors for colorectal cancer. Gastroenterology 2013;145:544-7.
16. Horpaopan S, Spier I, Zink AM, Altmüller J, Holzapfel S, Laner A, Vogt S, Uhlhaas S, Heilmann S, Stienen D, Pasternack SM, Keppler K, Adam R, Kayser K, Moebus S, Draaken M, Degenhardt F, Engels H, Hofmann A, Nöthen MM, Steinke V, Perez-Bouza A, Herms S, Holinski-Feder E, Fröhlich H, Thiele H, Hoffmann P, Aretz S. Genome-wide CNV analysis in 221 unrelated patients and targeted high-throughput sequencing reveal novel causative candidate genes for colorectal adenomatous polyposis. Int J Cancer 2015;136:E578-89.
17. Tuohy TM, Burt RW. Somatic mosaicism: a cause for unexplained cases of FAP? Gut 2008;57:10-12.
18. Macosko EZ, McCarroll SA. Exploring the variation within. Nat Genet 2012;44:614-16.
19. Moyhuddin A, Baser ME, Watson C, Purcell S, Ramsden RT, Heiberg A, Wallace AJ, Evans DG. Somatic mosaicism in neurofibromatosis 2: prevalence and risk of disease transmission to offspring. J Med Genet 2003;40:459-63.
20. Gammon A, Jasperson K, Pilarski R, Prior TW, Kuwada S. PTEN mosaicism with features of Cowden syndrome. Clin Genet 2013;84:593-5.
21. Campbell IM, Yuan B, Robberecht C, Pfundt R, Szafranski P, McEntagart ME, Nagamani SC, Erez A, Bartnik M, Wisniowiecka-Kowalnik B, Plunkett KS, Pursley AN, Kang SH, Bi W, Lalani SR, Bacino CA, Vast M, Marks K, Patton M, Olofsson P, Patel A, Veltman JA, Cheung SW, Shaw CA, Vissers LE, Vermeesch JR, Lupski JR, Stankiewicz P. Parental somatic mosaicism is underrecognized and influences recurrence risk of genomic disorders. Am J Hum Genet 2014;95: 173-82.
22. Necker J, Kovac M, Attenhofer M, Reichlin B, Heinimann K. Detection of APC germ line mosaicism in patients with de novo familial adenomatous polyposis: a plea for the protein truncation test. J Med Genet 2011;48:526-9.
23. Baert-Desurmont S, Piton N, Bou J, Tinat J, Guimbaud R, Selves J, Frébourg T. A remarkable APC mosaicism with two mutant alleles in a family with familial adenomatous polyposis. Am J Med Genet A 2011;155A:1500-2.
24. Filipe B, Albuquerque C, Bik E, Lage P, Rodrigues P, Vossen R, Tops C, Nobre Leitão C. APC somatic mosaicism in a patient with Gardner syndrome carrying the E1573X mutation: report of a case. Dis Colon Rectum 2009;52:1516-20; discussion 1520-1.
25. Schwab AL, Tuohy TM, Condie M, Neklason DW, Burt RW. Gonadal mosaicism and familial adenomatous polyposis. Fam Cancer 2008;7:173-7.
26. Yamaguchi K, Komura M, Yamaguchi R, Imoto S, Shimizu E, Kasuya S, Shibuya T, Hatakeyama S, Takahashi N, Ikenoue T, Hata K, Tsurita G, Shinozaki M, Suzuki Y, Sugano S, Miyano S, Furukawa Y. Detection of APC mosaicism by next-generation sequencing in an FAP patient. J Hum Genet 2015;60:227-31.
27. Aretz S, Stienen D, Friedrichs N, Stemmler S, Uhlhaas S, Rahner N, Propping P, Friedl W. Somatic APC mosaicism: a frequent cause of familial adenomatous polyposis (FAP). Hum Mutat 2007;28:985-92.
28. Hes FJ, Nielsen M, Bik EC, Konvalinka D, Wijnen JT, Bakker E, Vasen HF, Breuning MH, Tops CM. Somatic APC mosaicism: an underestimated cause of polyposis coli. Gut 2008;57:71-6.
29. Freed D, Stevens EL, Pevsner J. Somatic mosaicism in the human genome. Genes (Basel) 2014;5:1064-94.
30. Rohlin A, Wernersson J, Engwall Y, Wiklund L, Björk J, Nordling M. Parallel sequencing used in detection of mosaic mutations: comparison with four diagnostic DNA screening techniques. Hum Mutat 2009;30:1012-20.
31. Aretz S, Stienen D, Uhlhaas S, Pagenstecher C, Mangold E, Caspari R, Propping P, Friedl W. Large submicroscopic genomic APC deletions are a common cause of typical familial adenomatous polyposis. J Med Genet 2005;42:185-92.
32. Michils G, Tejpar S, Thoelen R, Cutsem E, Vermeesch JR, Fryns J-P, Legius E, Matthijs G. Large deletions of the APC gene in 15% of mutation-negative patients with classical polyposis (FAP): a Belgian study. Hum Mutat 2005;25:125-34.
33. Schweiger MR, Kerick M, Timmermann B, Albrecht MW, Borodina T, Parkhomchuk D, Zatloukal K, Lehrach H. Genome-wide massively parallel sequencing of formaldehyde fixed-paraffin embedded (FFPE) tumor tissues for copy-number-and mutation-analysis. PLoS ONE 2009;4:e5548.
34. Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR, Zumbo P, Nayir A, Bakkaloglu A, Ozen S, Sanjad S, Nelson-Williams C, Farhi A, Mane S, Lifton RP. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci USA 2009;106:19096-101.
35. Kerick M, Isau M, Timmermann B, Sültmann H, Herwig R, Krobitsch S, Schaefer G, Verdorfer I, Bartsch G, Klocker H, Lehrach H, Schweiger MR. Targeted high throughput sequencing in clinical cancer settings: formaldehyde fixed-paraffin embedded (FFPE) tumor tissues, input amount and tumor heterogeneity. BMC Med Genomics 2011;4:68.
36. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 2009;25:1754-60.
37. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M, Depristo MA. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 2010;20:1297-303.
38. Wang K, Li M. Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 2010;38:e164.
39. Kohler EM, Derungs A, Daum G, Behrens J, Schneikert J. Functional definition of the mutation cluster region of adenomatous polyposis coli in colorectal tumours. Hum Mol Genet 2008;17:1978-87.
40. Out AA, van Minderhout IJHM, van der Stoep N, Van Bommel LSR, Kluijt I, Aalfs C, Voorendt M, Vossen RHAM, Nielsen M, Vasen HFA, Morreau H, Devilee P, Tops CMJ, Hes FJ. High-resolution melting (HRM) re-analysis of a polyposis patients cohort reveals previously undetected heterozygous and mosaic APC gene mutations. Fam Cancer 2015;14:247-57.