Hereditary mixed polyposis syndrome is caused by a 40-kb upstream duplication that leads to increased and ectopic expression of the BMP antagonist GREM1

Nature Genetics

Volumn 44, Issue 6, 2012, Pages 699-703

  Jaeger, Emma ^a   Leedham, Simon ^a,b   Lewis, Annabelle ^a   Segditsas, Stefania ^a   Becker, Martin ^a   Cuadrado, Pedro Rodenas ^a   Davis, Hayley ^a   Kaur, Kulvinder ^c   Heinimann, Karl ^a,d   Howarth, Kimberley ^a   East, James ^b   Taylor, Jenny ^c   Thomas, Huw ^e   Tomlinson, Ian ^a,c  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b JOHN RADCLIFFE HOSPITAL   (United Kingdom)

^c UNIVERSITY OF OXFORD   (United Kingdom)

^d Universitaetskinderspital Beider Basel   (Switzerland)

^e ST MARK S HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BONE MORPHOGENETIC PROTEIN;

ARTICLE; AUTOSOMAL DOMINANT INHERITANCE; COLON CARCINOGENESIS; COLORECTAL CARCINOMA; COLORECTAL POLYP; CONTROLLED STUDY; GENE; GENE DUPLICATION; GENE EXPRESSION; GENE LOCUS; GENE MAPPING; GENE MUTATION; GENE SEQUENCE; GREM1 GENE; HEREDITARY MIXED POLYPOSIS SYNDROME; HUMAN; HUMAN CELL; HUMAN TISSUE; POLYPOSIS; PRIORITY JOURNAL; PROMOTER REGION;

BONE MORPHOGENETIC PROTEINS; CHROMOSOME MAPPING; CHROMOSOMES, HUMAN, PAIR 15; COLONIC POLYPS; COLORECTAL NEOPLASMS; DNA COPY NUMBER VARIATIONS; FETAL PROTEINS; GENE DUPLICATION; GENE EXPRESSION; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; MICROFILAMENT PROTEINS; NEUROENDOCRINE SECRETORY PROTEIN 7B2; NUCLEAR PROTEINS; RECEPTORS, IMMUNOLOGIC; SYNDROME;

EID: 84861584357     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng.2263     Document Type: Article

References (21)

1. Whitelaw, S.C. et al. Clinical and molecular features of the hereditary mixed polyposis syndrome. Gastroenterology 112, 327-334 (1997). (Pubitemid 27078819)
2. Jaeger, E.E. et al. An ancestral Ashkenazi haplotype at the HMPS/CRAC1 locus on 15q13-q14 is associated with hereditary mixed polyposis syndrome. Am. J. Hum. Genet. 72, 1261-1267 (2003). (Pubitemid 36530012)
3. Tomlinson, I. et al. Inherited susceptibility to colorectal adenomas and carcinomas: evidence for a new predisposition gene on 15q14-q22. Gastroenterology 116, 789-795 (1999). (Pubitemid 29153526)
4. Jaeger, E. et al. Common genetic variants at the CRAC1 (HMPS) locus on chromosome 15q13.3 influence colorectal cancer risk. Nat. Genet. 40, 26-28 (2008).
5. Cheah, P.Y. et al. Germline bone morphogenesis protein receptor 1A mutation causes colorectal tumorigenesis in hereditary mixed polyposis syndrome. Am. J. Gastroenterol. 104, 3027-3033 (2009).
6. East, J.E., Saunders, B.P. & Jass, J.R. Sporadic and syndromic hyperplastic polyps and serrated adenomas of the colon: classification, molecular genetics, natural history, and clinical management. Gastroenterol. Clin. North Am. 37, 25-46, v (2008). (Pubitemid 351289032)
7. Colella, S. et al. QuantiSNP: an Objective Bayes Hidden-Markov Model to detect and accurately map copy number variation using SNP genotyping data. Nucleic Acids Res. 35, 2013-2025 (2007). (Pubitemid 47061667)
8. Tomlinson, I.P. et al. COGENT (COlorectal cancer GENeTics): an international consortium to study the role of polymorphic variation on the risk of colorectal cancer. Br. J. Cancer 102, 447-454 (2010).
9. Kosinski, C. et al. Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors. Proc. Natl. Acad. Sci. USA 104, 15418-15423 (2007). (Pubitemid 47502932)
10. Segditsas, S. et al. Putative direct and indirect Wnt targets identified through consistent gene expression changes in APC-mutant intestinal adenomas from humans and mice. Hum. Mol. Genet. 17, 3864-3875 (2008). (Pubitemid 352762849)
11. Tomlinson, I.P. et al. Multiple common susceptibility variants near BMP pathway loci GREM1, BMP4, and BMP2 explain part of the missing heritability of colorectal cancer. PLoS Genet. 7, e1002105 (2011).
12. Tian, Q., He, X.C., Hood, L. & Li, L. Bridging the BMP and Wnt pathways by PI3 kinase/Akt and 14-3-3ζ. Cell Cycle 4, 215-216 (2005). (Pubitemid 41365318)
13. Hobert, J.A. & Eng, C. PTEN hamartoma tumor syndrome: an overview. Genet. Med. 11, 687-694 (2009).
14. Venkatachalam, R. et al. Identification of candidate predisposing copy number variants in familial and early-onset colorectal cancer patients. Int. J. Cancer 129, 1635-1642 (2011).
15. Papaemmanuil, E. et al. Deciphering the genetics of hereditary non-syndromic colorectal cancer. Eur. J. Hum. Genet. 16, 1477-1486 (2008).
16. Zuniga, A. et al. Mouse limb deformity mutations disrupt a global control region within the large regulatory landscape required for Gremlin expression. Genes Dev. 18, 1553-1564 (2004). (Pubitemid 38868907)
17. Howe, J.R. et al. Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. Nat. Genet. 28, 184-187 (2001). (Pubitemid 32538067)
18. Howe, J.R. et al. Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science 280, 1086-1088 (1998). (Pubitemid 28234951)
19. Lo, H.S. et al. Allelic variation in gene expression is common in the human genome. Genome Res. 13, 1855-1862 (2003). (Pubitemid 36987191)
20. Poulsom, R., Longcroft, J.M., Jeffery, R.E., Rogers, L.A. & Steel, J.H. A robust method for isotopic riboprobe in situ hybridisation to localise mRNAs in routine pathology specimens. Eur. J. Histochem. 42, 121-132 (1998). (Pubitemid 28362310)
21. Miele, A., Gheldof, N., Tabuchi, T.M., Dostie, J. & Dekker, J. Mapping chromatin interactions by chromosome conformation capture. Curr. Protoc. Mol. Biol. Chapter 21, Unit 21.11 (2006).