English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  β-catenin activation plays a crucial role for tumourigenesis in the large intestine but except for Lynch syndrome (LS) associated cancers stabilizing mutations of  β-catenin  gene ( CTNNB1)  are rare in colorectal cancer (CRC). Previous animal studies provide an explanation for this observation. They showed that  CTNNB1  mutations induced transformation in the colon only when  CTNNB1  was homozygously mutated or when membranous β-catenin binding was hampered by E-cadherin haploinsufficiency. We were interested, if these mechanisms are also found in human  CTNNB1  mutated CRCs.    Results  Among 869 CRCs stabilizing  CTNNB1  mutations were found in 27 cases. Homo- or hemizygous  CTNNB1  mutations were detected in 74% of  CTNNB1  mutated CRCs (13 microsatellite instabile (MSI-H), 7 microsatellite stabile (MSS)) but only in 3% (1/33) of extracolonic  CTNNB1  mutated cancers. In contrast to MSS CRC,  CTNNB1  mutations at codon 41 or 45 were highly selected in MSI-H CRC. Of the examined three CRC cell lines, β-catenin and E-cadherin expression was similar in cell lines without or with hetereozygous  CTNNB1  mutations (DLD1 and HCT116), while a reduced E-cadherin expression combined with cytoplasmic accumulation of β-catenin was found in a cell line with homozygous  CTNNB1  mutation (LS180). Reduced expression of E-cadherin in human MSI-H CRC tissue was identified in 60% of investigated cancers, but no association with the  CTNNB1  mutational status was found.    Conclusions  In conclusion, this study shows that in contrast to extracolonic cancers stabilizing  CTNNB1  mutations in CRC are commonly homo- or hemizygous indicating a higher threshold of β-catenin stabilization to be required for transformation in the colon as compared to extracolonic sites. Moreover, we found different mutational hotspots in  CTNNB1  for MSI-H and MSS CRCs suggesting a selection of different effects on β-catenin stabilization according to the molecular pathway of tumourigenesis. Reduced E-cadherin expression in CRC may further contribute to higher levels of transcriptionally active β-catenin, but it is not directly linked to the  CTNNB1  mutational status.    Supplementary information   Supplementary information  accompanies this paper at 10.1186/s12885-020-07537-2.

The majority of β-catenin mutations in colorectal cancer is homozygous