Wnt signalling in adenomas of familial adenomatous polyposis patients.

British Journal of Cancer
G M CaldwellG M Matthews

Abstract

Epigenetic silencing of Wnt antagonists and expression changes in genes associated with Wnt response pathways occur in early sporadic colorectal tumourigenesis, indicating that tumour cells are more sensitive to Wnt growth factors and respond differently. In this study, we have investigated whether similar changes occur in key markers of the Wnt response pathways in the genetic form of the disease, familial adenomatous polyposis (FAP). We investigated epigenetic and expression changes using pyrosequencing and real-time RT-PCR in samples from seven patients without neoplasia, and matched normal and tumour tissues from 22 sporadic adenoma and 14 FAP patients. We found that 17 out of 24 (71%) FAP adenomas were hypermethylated at sFRP1, compared with 20 out of 22 (91%) of sporadic cases. This was reflected at the level of sFRP1 transcription, where 73% of FAP and 100% of sporadic cases were down-regulated. Increased expression levels of c-myc and FZD3 were less common in FAP (35 and 46% respectively) than sporadic tumours (78 and 67% respectively). Overall, the changes in expression and methylation were comparable, although the degree of change was generally lower in the FAP adenomas. Molecular heterogeneity between multiple adenom...Continue Reading

References

Mar 21, 2001·Human Molecular Genetics·N S FearnheadW F Bodmer
Mar 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·D YanL T Williams
Jun 20, 2002·Proceedings of the National Academy of Sciences of the United States of America·Christine B AndersonRaymond L White
Feb 12, 2004·Cancer Research·Germaine M CaldwellDion G Morton
Mar 9, 2006·British Journal of Cancer·G M CaldwellD G Morton
Apr 6, 2007·Gastroenterology·Kazuo KonishiJean-Pierre J Issa
May 9, 2007·Molecular and Cellular Biology·Victoria H CowlingMichael D Cole
Apr 17, 2008·British Journal of Cancer·G M CaldwellG M Matthews
Mar 3, 2010·The Journal of Pathology·Antònia Obrador-HeviaGabriel Capellá

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Citations

Nov 21, 2013·PloS One·Sze Chuen Cesar WongAnthony Tak Cheung Chan
Sep 19, 2014·Journal of the Royal Society, Interface·Chunhe Li, Jin Wang
Aug 22, 2014·PLoS Computational Biology·Victor J BarrancaDavid Cai
Jul 27, 2012·International Journal of Cancer. Journal International Du Cancer·Koji UenoRajvir Dahiya

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Methods Mentioned

BETA
biopsies
PCR

Software Mentioned

R

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